Preparation of core–shell type nanoparticles of diblock copolymers of poly(L‐lactide)/poly(ethylene glycol) and their characterization in vitro

Core–shell type nanoparticles of poly(L ‐lactide)/poly(ethylene glycol) (LE) diblock copolymer were prepared by a dialysis technique. Their size was confirmed as 40–70 nm using photon correlation spectroscopy. The ¹H‐NMR analysis confirmed the formation of core–shell type nanoparticles and drug loading. The particle size, drug loading, and drug release rate of the LE nanoparticles were slightly changed by the initial solvents that were used. The drug release behavior of LE core–shell type nanoparticles showed an initial burst during the first 12 h and then a sustained release until 100 h. The degradation behavior of LE block copolymer nanoparticles was divided into three phases: the initial rapid degradation phase, the stationary phase, and the rapid degradation phase until complete degradation. It was suggested that lidocaine release kinetics were predominantly governed by the diffusion mechanism in the initial burst phase and after that by both of the diffusion and degradation mechanisms. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2625–2634, 2002     

Complementary Tasks to Measure Working Memory in Distinct Prefrontal Cortex Subregions in Rats.

Acquisition of odor-guided or visually-guided delayed win-shift behavior was evaluated in rats after lidocaine-induced inactivation within the agranular insular area of the prefrontal cortex (PFC) or the prelimbic area of the PFC. Additional sites and tasks were used to control for neuroanatomical and behavioral specificity of lidocaine inactivation of the agranular insular and prelimbic areas. Results showed that acquisition of the odor-guided delayed win-shift task was dependent on the agranular insular area, whereas acquisition of the visually-guided version was dependent on the prelimbic area. This dissociation suggests that the stimulus modality used is critical for revealing working memory functions of different PFC subregions. The described methods provide a complementary means to study working memory in PFC subregions using a radial-arm maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

Recent findings indicate that neonatal injury results in decreased spinal plasticity in adult subjects (E. E. Young, K. M. Baumbauer, A. E. Elliot, & R. L. Joynes, 2007). Previous research has shown that acute manipulations of pain processing (i.e., administration of formalin, carrageenan, capsaicin) result in a loss of spinal behavioral plasticity (A. R. Ferguson, E. D. Crown, & J. W. Grau, 2006). Moreover, neonatal injury results in a lasting reduction in adult spinally mediated plasticity resembling the deficit seen following acute manipulations in adults (E. E. Young et al., 2007). The present study was designed to determine whether the effects of neonatal injury could be prevented by lidocaine administration during the initial healing period. Subjects (injured or uninjured) received lidocaine or saline on 1 of 4 administration schedules (preinjury only, postinjury only, for 24 hr postsurgery, or for 72 hr postsurgery). Results demonstrated that lidocaine administration did not prevent the hypersensitivity and reduced spinal plasticity associated with neonatal injury. This suggests that (a) the mechanisms underlying neonatal injury are independent of peripheral input in the initial healing period and (b) lidocaine is ineffective at preventing long-term spinal plasticity changes following neonatal injury. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

流动注射化学发光法测定盐酸利多卡因

基于盐酸利多卡因对鲁米诺-过氧化氢化学发光反应的增敏作用,结合流动注射技术,建立了流动注射化学发光反应测定盐酸利多卡因的新方法。该方法的线性范围为8．0×10^-8～5．0×10^-6g／mL,检出限为1．2×10^-4g／mE。对5．0×10^-7g／mE的盐酸利多卡因进行11次平行测定,相对标准偏差2．5％,方法简单、快速、灵敏。该法已用于针剂中盐酸利多卡因含量的测定。     

Acute pain responses in dairy calves undergoing cornual nerve blocks with or without topical anesthetic

Dairy calves are routinely administered medicines, vaccines, and anesthesia via injection. Although injections are painful, little is known about methods to alleviate this pain. The aim of this study was to determine whether lidocaine–prilocaine cream, a topical anesthetic, reduced calves' pain response to a subcutaneous injection around the cornual nerve. Calves were assigned 1 of 2 treatments: lidocaine–prilocaine cream at the sites of injection (n = 10) or no cream (n = 9). Thirty minutes after treatment, calves received a subcutaneous injection of 2% buffered lidocaine hydrochloride around the left and right cornual nerves. Contrary to our hypothesis, calves that received anesthetic cream beforehand displayed more escape behaviors during the injections than control calves. Both treatments had similarly low amounts of head-related behaviors afterward. Maximum eye temperature did not differ between the calves that received anesthetic cream and control calves, although eye temperature increased over time for both treatments. Heart rate increased during the 30 s following the first injection in both treatments. There were no treatment differences for any heart rate measures over the 5-min period after the first injection (mean heart rate, root mean square of successive differences, high-frequency power, and the ratio of low-frequency power to high-frequency power). These results suggest that cornual nerve blocks with buffered lidocaine are painful and that a lidocaine–prilocaine cream was not only ineffective in reducing this pain but that it may also worsen it.     

Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization

The aim of this study was to characterize a buccal mucoadhesive film using lidocaine and its hydrochloride salt (LDHCL) as a model drug. Buccal films were developed using carbopol 971P as a mucoadhesive polymer, and glycerol as a plasticizer. Scanning Electron Microscope, Differential Scanning Calorimetry, X-ray powder diffraction, and Fourier Transform Infra Red techniques were used to characterize the mucoadhesive films. Bioadhesive properties were evaluated using the Universal Instron Instrument with chicken pouch as a model tissue.

LDHCL and its base were present in carbopol 971P films in a molecular dispersion state without exerting any effect on the glass transition of these films. The mucoadhesive force between the chicken pouches and the film containing glycerol did not change by time during the tested period (1-20 min), while increased with increasing the amount of glycerol (10-40% w/w of polymer content). Furthermore, a linear increase in the mucoadhesive force was accompanied by the increase in the film thickness, while a linear decrease followed by plateau was obtained when loading the patch with LDHCL at concentration above 1 mg/cm².

Loading carbopol film with lidocaine base, in a concentration up to 6 mg/cm² decreased linearly the mucoadhesive properties, which could be attributed to salt formation between the acidic carboxylic moiety of carbopol and basic lidocaine.     

Effects of a concentrated lidocaine solution on the acute phase stress response to dehorning in dairy calves

The objective of this study was to more fully define the surgical stress response to dehorning by heat cauterization in dairy calves by measuring behavioral, hormonal, inflammatory, and immunological markers of stress and to determine whether a nerve block of the surgical site with a concentrated solution of lidocaine (5%) reduces the degree of stress. Thirty-two 10- to 12-wk-old female Holstein calves were randomly allotted to 1 of 4 treatments: 5% lidocaine followed by dehorning, 2% lidocaine followed by dehorning, saline followed by dehorning, or 5% lidocaine followed by sham dehorning. Plasma cortisol concentration was measured in blood samples collected via a jugular catheter at −0.5, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48, and 72 h. Various other blood constituents were measured in samples collected at −0.5, 12, 24, 48, and 72 h. Feeding, drinking, scratching, grooming, rubbing, licking, and inactivity behaviors were observed in the standing and recumbent positions using a 10-min scan sampling method analyzed on a time period and daily basis for 72 h following the dehorning procedure. The frequency of vocalization, kicking, and lying in the chute during the dehorning procedure were also assessed. The overall plasma cortisol concentrations were higher in calves subjected to dehorning than in control calves. Compared with the control group, the saline-treated calves had a higher cortisol concentration at 30 and 60 min postdehorning. Plasma cortisol concentrations were higher in all groups at 30 min postdehorning than at other sampling times. The percentage of circulating neutrophils and the neutrophil:lymphocyte ratio were increased in the saline and 2% lidocaine group. Total plasma protein, fibrinogen, and α₁-acid glycoprotein concentrations were similar among treatments. The behavioral response to dehorning, as manifested by kicking while in the chute, was greater in the saline and 2% lidocaine group than in the control or 5% lidocaine treatment groups. In the postdehorning period, the percentage of time calves spent performing various maintenance behaviors did not differ among treatments. Thus, injection of 5% lidocaine may not provide any added comfort after the dehorning but may decrease the overall stress response during the procedure.     

高原地区碳酸利多卡因在剖宫产术中的临床应用

目的:比较在高原地区不同麻醉方法用于剖宫产手术的麻醉效果及安全性。方法:选择60例行剖宫产手术患者,ASA I～II级, 随机分为2%盐酸利多卡因组(I组, 选择L1～2间隙行硬膜外穿刺向上置管3～4cm), 1.73%碳酸利多卡因组(II组, 麻醉穿刺方法同I组)和0.5%布比卡因重比重溶液组(III组, 选择L3～4间隙穿刺行腰硬联合阻滞)三组。比较三组间麻醉起效时间、麻醉完善时间、麻醉最高平面, 胎儿娩出时间, 记录麻醉对患者血压、心率的影响及患者的不良反应。结果:II组与I组比较麻醉起效快, 麻醉完善时间短, 胎儿娩出时间短;与III组比较对患者心率、血压影响小, 患者不良反应少, 差异有统计学意义。结论:高原地区低氧环境下在剖宫产手术中用碳酸利多卡因行硬膜外麻醉具有麻醉起效快、麻醉完善时间短、效果确切的特点, 而且对患者血流动力学影响小, 不良反应少, 提高了母婴术中安全性,是一种更为安全、可靠的麻醉方法。     

Inactivation of Dorsolateral Striatum Impairs Acquisition of Response Learning in Cue-Deficient, but Not Cue-Available, Conditions.

Rats received bilateral injections of lidocaine or artificial cerebrospinal fluid (aCSF) into the doisolateral striatum 6 min prior to training in either a plus- or T-shaped maze under cue-poor or cue-available conditions. Lidocaine injections significantly impaired acquisition in the cue-poor environments, but not in the cue-available environments. In addition, aCSF control rats trained in a plus-maze in a cue-poor environment reached criterion much more rapidly than did rats trained in a cue-available environment. These findings suggest that cue availability can permit acquisition of response learning in a manner that is not dependent on activity of the striatum. However, in a cue-poor environment, alternate strategies may be less readily available, revealing more efficient striatal involvement in response learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lidocaine induces endoplasmic reticulum stress-associated apoptosis in vitro and in vivo

We demonstrated that upregulation of both gene expression of endoplasmic reticulum (ER) stress chaperones (BiP, calnexin, calreticulin, and PDI) and ER stress sensors (ATF6, IRE1 and PERK) was induced by lidocaine, a local anesthetic, in PC12 cells. In addition to gene regulation, lidocaine also induced typical ER stress phenomena such as ART6 proteolytic cleavage, eIF2 alpha phosphorylation, and XBP1 mRNA splicing. In in vivo experiments, while lidocaine downregulated gene expression of antiapoptotic factors (Bcl-2 and Bcl-xl), pro-apoptotic factor (Bak and Bax) gene expression was upregulated. Furthermore, lidocaine induced apoptosis, as measured histochemically, and upregulated PARP1, a DNA damage repair enzyme. These results are the first to show that lidocaine induces apoptosis through ER stress in vitro and in vivo.