A distinct cortical code for socially learned threat.

Animals can learn about sources of danger while minimizing their own risk by observing how others respond to threats. However, the distinct neural mechanisms by which threats are learned through social observation (known as observational fear learning1-4 (OFL)) to generate behavioural responses specific to such threats remain poorly understood. The dorsomedial prefrontal cortex (dmPFC) performs several key functions that may underlie OFL, including processing of social information and disambiguation of threat cues5-11. Here we show that dmPFC is recruited and required for OFL in mice. Using cellular-resolution microendoscopic calcium imaging, we demonstrate that dmPFC neurons code for observational fear and do so in a manner that is distinct from direct experience. We find that dmPFC neuronal activity predicts upcoming switches between freezing and moving state elicited by threat. By combining neuronal circuit mapping, calcium imaging, electrophysiological recordings and optogenetics, we show that dmPFC projections to the midbrain periaqueductal grey (PAG) constrain observer freezing, and that amygdalar and hippocampal inputs to dmPFC opposingly modulate observer freezing. Together our findings reveal that dmPFC neurons compute a distinct code for observational fear and coordinate long-range neural circuits to select behavioural responses.

Injectable testosterone PLGA microsphere with different characteristics: effect of preparation method (paddle mixing versus microfluidic device).

The purpose of this study was to compare the characteristics of testosterone polylactic-co-glycolic (PLGA) microspheres prepared by a paddle mixer or microfluidics device. The comparison was conducted by not only in vitro evaluation but also in vivo evaluation which has not been reported up to date. We discovered that, among the steps in microsphere preparation, the solvent removal process strongly impacted drug content, particle size and surface morphology. Spectroscopic measurements suggested that molecular interactions and crystallinity of the drug incorporated in the microspheres differed. For the drug release profile, although both mixer- and microfluidics-prepared samples showed similar sustained release of the incorporated drug for approximately one month in vitro, they exhibited different plasma concentration profiles in vivo. Together, our findings show that the preparation process, especially the solvent removal process, may affect the physicochemical characteristics of testosterone PLGA microspheres, leading to different in vivo performance.

Oral Drug Delivery Systems Applied to Launched Products: Value for the Patients and Industrial Considerations.

Drug delivery systems (DDS) control the amount, rate, and site of administration of drug substances in the body as well as their release and ADME (absorption, distribution, metabolism, excretion). Among the various types of DDS, amount-controlled DDS for solubilization and absorption increase the bioavailability. Time- and amount-controlled DDS are controlled release formulations classified as (1) membrane-type, (2) matrix-type, (3) osmotic-type, and (4) ion-exchange type. Timed-release formulations also control the time and amount of release and the absorption of drugs. Site- and amount-controlled DDS are characterized by colonic delivery and intestinal lymph-targeting to improve release and ADME of drug substances. Finally, site-, time-, and amount-controlled DDS are gastroretentive formulations and local delivery in the oral cavity to improve site retention, release, and ADME of drugs. DDS can enhance efficacy, reduce adverse effects, and optimize the dosing frequency of various drug products to increase patient value. This review focuses on patient value and industrial considerations of launched oral DDS. We provide a technological overview of candidate and marketed DDS, as well as the pros/cons of the technologies for industrialization with consideration to excipients, manufacturing, and storage stability. Moreover, to demonstrate the usefulness of the technology and support the selection and development of the best technologies for patients, we also describe patient value from clinical studies and analyses, particularly with regard to increased new medical options, higher efficacy, reduced adverse effects, reduced number of doses and clinic visits, easier administration, higher quality of life, greater adherence, and satisfaction.

Drug Extended-Release System Utilizing Micelle Formation of Highly Water-Soluble Drugs and a Counter Polymer.

The objective of this study is to clarify the mechanism of extending release of highly water-soluble drugs via counter polymer (CP) utilization in poly(ethylene oxide) (PEO)/polyethylene glycol (PEG) matrix tablets. Carbomer, poly(acrylic acid), was used as a CP, which has the opposite charges to the drugs. The in vitro release of several highly water-soluble drugs from PEO/PEG tablet with or without CP were tested, the relationship between the sustained release effect by a CP (SRE) and the physicochemical properties of the drugs was investigated. The results demonstrated that the utilization of CP can extend the release of some highly water-soluble drugs by effectively controlling the drug diffusion through matrices. On the other hand, the effectiveness of CP was different depending on the drugs applied. There were not statistical correlations between SRE and physicochemical properties such as solubility, molecular weight, and charge intensity of the drugs, while a micelle forming property of the drugs played an important role in SRE by CP. It was concluded that CP, Carbomer, having negative charges could effectively interact with opposite charges on the surface of stable drug micelles, which could result in a significant decrease in drug diffusion leading to extended drug release. It is considered that the system utilizing CP is a promising approach to achieve extended release of highly water-soluble drugs with a reasonable tablet size, especially in the case of large drug loading.

Visualizing fluid transport inside orally disintegrating tablets and changes in tablets using real-time X-ray radiography and X-ray computed tomography.

OBJECTIVE: To investigate the disintegration of wet- and dry-compressed orally disintegrating (OD) tablets, with synchrotron radiation as the X-ray source. SIGNIFICANCE: Pharmaceutical tablets are vital for the treatment of various diseases. Therefore, they are constantly developed to ensure desirable characteristics. In particular, OD tablets need to disintegrate immediately after absorbing saliva. How these tablets absorb saliva is key to enhancing rapid product development. Recently, absorption processes have been investigated using various noninvasive techniques, including X-ray radiography and X-ray computed tomography. However, X-ray radiography studies on how water without a contrast agent is absorbed, moves, and causes a tablet to swell are scarce. The use of a contrast agent is associated with some shortcomings, including complex data analysis in some instances, alterations in the viscosity of water, and potential influence on fluid transport inside the tablet, thus possibly affecting the disintegration process. METHODS: Real-time X-ray radiography was used to monitor the disintegration of various tablets, while X-ray computed tomography and software were used to create 3 D images. RESULTS: We demonstrated how pure water penetrated the wet-compressed tablet faster than inside the dry-compressed tablet, and how the latter swelled more. X-ray computed tomography showed the presence of voids in the tablets following water absorption. CONCLUSION: Our methods are promising for nondestructive fluid absorption and transport investigations inside OD tablets.

Drug delivery to the intestinal lymph by oral formulations.

Oral drug delivery systems (DDS) targeting lymphocytes in intestinal lymphatic vessels, ducts, and nodes are useful for treating diverse diseases. The intestinal lymph harbors numerous lymphocyte subsets, and DDS containing lipids such as triglycerides and fatty acids can deliver drugs to the lymph through the chylomicron pathway. DDS are efficient, thus allowing the administration of reduced drug doses, which mitigate systemic adverse effects. Here we review orally administered lipid formulations comprising oil solutions, suspensions, micro/nanoemulsions, self-micro/nano emulsifying DDS, liposomes, micelles, solid lipid nanoparticles, and nanostructured lipid carriers for targeting drugs to the lymph. We first describe the structures of lymphatic vessels and lymph nodes and the oral absorption of lipids and drugs into the intestinal lymph. We next summarize the effects of the properties and amounts of lipids and drugs delivered into the lymph and lymphocytes, as well as their effects on drug delivery ratios of lymph to blood. Finally, we describe lymphatic DDS containing saquinavir, tacrolimus, and methotrexate, and their potency that reduces drug concentrations in blood, which are associated with systemic adverse effects.

[Methods for Recovering Residual Anticancer Drugs in Medical Settings to Improve Working Environments].

We examined the methods for recovering residual anticancer drugs in medical settings to prevent health hazards caused by exposure to anticancer drugs. Presently, the lactose hydrate recovery rates(Lac, an alternative sample for an anticancer drug)were determined using 2 drug recovery methods that are based on a procedure manual(procedure manual method) and smart remote support(remote support method). Using the procedure manual method, 5 healthcare workers recovered Lac after receiving a detailed face-to-face methodological explanation. Using the remote support method, 3 healthcare workers recovered Lac regarded by an instructor waiting at a remote site without using a procedure manual. As a result, the Lac recovery rates were>80% for both methods; however, they showed the need for improvement. Eventually, the issues found presently will be resolved to improve the working environments of healthcare workers, caregivers, and medical service providers.

Serotonin neurons in the median raphe nucleus bidirectionally regulate somatic signs of nicotine withdrawal in mice.

In chronic smokers, nicotine withdrawal symptoms during tobacco cessation can lead to smoking relapse. In rodent models, chronic exposure to nicotine elicited physical dependence, whereas acute antagonism of nicotinic acetylcholine receptors (nAChRs) immediately precipitated withdrawal symptoms. Although the central serotonergic system plays an important role in nicotine withdrawal, the exact serotonergic raphe nuclei regulating these symptoms remain unknown. We used transgenic mice expressing archaerhodopsinTP009 or channelrhodopsin-2[C128S] exclusively in the central serotonergic neurons to selectively manipulate serotonergic neurons in each raphe nucleus. Nicotine withdrawal symptoms were precipitated by an acute injection of mecamylamine, a nonspecific nAChR antagonist, following chronic nicotine consumption. Somatic signs were used as measures of nicotine withdrawal symptoms. Acute mecamylamine administration significantly increased ptosis occurrence in nicotine-drinking mice compared with that in control-drinking mice. Optogenetic inhibition of the serotonergic neurons in the median raphe nucleus (MRN), but not of those in the dorsal raphe nucleus (DRN), mimicked the symptoms observed during mecamylamine-precipitated nicotine withdrawal even in nicotine-naïve mice following the administration of acute mecamylamine injection. Optogenetic activation of the serotonergic neurons in the MRN nearly abolished the occurrence of ptosis in nicotine-drinking mice. The serotonergic neurons in the MRN, but not those in the DRN, are necessary for the occurrence of somatic signs, a nicotine withdrawal symptom, and the activation of these neurons may act as a potential therapeutic strategy for preventing the somatic manifestations of nicotine withdrawal.

Enantioselective Protonation of Cyclic Carbonyl Ylides by Chiral Lewis Acid Assisted Alcohols.

Chiral Lewis acid-catalyzed asymmetric alcohol addition reactions to cyclic carbonyl ylides generated from N-(α-diazocarbonyl)-2-oxazolidinones featuring a dual catalytic system are reported. Construction of a chiral quaternary heteroatom-substituted carbon center was accomplished in which the unique heterobicycles were obtained in good yields with high stereoselection. The alcohol adducts were successfully converted to optically active oxazolidine-2,4-diones by hydrolysis. Mechanistic studies by DFT calculations revealed that alcohols could be activated by Lewis acids, enabling enantioselective protonation of the carbonyl ylides.

The effect of perception of seat width on back-to-sit task.

[Purpose] The movement trajectory in daily motion is strongly associated with information regarding the properties of the environment. In the case of the back-to-sit task, it may vary according to chair property. The purpose of this study was to investigate whether trajectory formation in back-to-sit tasks by healthy adults depends on seat width information. [Participants and Methods] Ten healthy young males performed a back-to-sit task in 5 seat width conditions (80%, 90%, 100%, 110%, and 120% of each participant's buttock breadth). The motion analysis system and force plates were set at a sampling frequency of 250 Hz. The spatial and temporal variables were calculated to examine the effect of seat width. A questionnaire was also administered to examine whether the participants were aware of each seat width in comparison with their own buttock breadth as narrow or large. [Results] The questionnaire results showed that many participants were aware but some were unaware of the relative comparison of their size to the seat width. Nevertheless, the spatial and temporal variables were invariant under the different seat width conditions. [Conclusion] In healthy adults, the trajectory formation in back-to-sit tasks is not dependent on the perception of seat width information under their variability as per daily situations.

Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.

Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.

Design of novel tacrolimus formulations with chemically synthesized oils for oral lymphatic delivery.

High consumption of oil formulations has been reported to reduce the blood exposure of drugs like tacrolimus. Consumption of oil formulations has also been shown to inhibit T-cell production of interleukin-2 (IL-2) compared to solid dispersion formulations (SDFs). However, a large amount of oil causes gastrointestinal side effects such as diarrhea and low compliance. Here, we investigated the feasibility of reducing the amount of oil and substitution of chemically synthetized oils for natural oils in these formulations. Reducing the amount of sunflower oil increased blood tacrolimus exposure despite sufficient suppression of IL-2 production. While medium-chain triglyceride (MCT) increased tacrolimus blood exposure, addition of 10% glyceryl monostearate (GMS) to MCT significantly decreased drug blood exposure without requiring a large amount of oil (p < .05). Effects of the contents of GMS in the MCT/GMS formulations, and fatty acid composition in GMS on drug blood exposure were also investigated. The results indicated that both the amount and type of oil were important for maintaining a good balance between a reduction in blood exposure and sufficient IL-2 suppression. The ratio of drug concentration in lymphocytes to that in whole blood after dosing with an oil formulation was significantly higher than that after administration of the SDF (p < .01). These results indicate the feasibility of developing oral oil tacrolimus formulations to reduce systemic side effects and maintain high efficacy for practical use in patients.

JTE-607, a multiple cytokine production inhibitor, targets CPSF3 and inhibits pre-mRNA processing.

JTE-607 is a small molecule that was developed as an inflammatory cytokine inhibitor and also as an anti-leukemia reagent for monocytic leukemia. However, the mode of action of JTE-607 remains unknown. In this study, we identified JTE-607 to be a prodrug compound that is converted to an active form by ester hydrolysis. Furthermore, we determined that the active form of JTE-607 bound cleavage and polyadenylation specificity factor subunit 3 (CPSF3), using compound-immobilized affinity chromatography. CPSF3 is a 73-kDa subunit of the cleavage and polyadenylation specificity factor complex, which functions as an RNA endonuclease. The protein is involved in the 3'-end processing of messenger RNA precursors (pre-mRNAs) at the cleavage site located downstream of the poly(A) addition signal. We found that treatment with JTE-607 caused accumulation of pre-mRNAs. Furthermore, knockdown experiments showed that CPSF3 deficiency also caused accumulation of pre-mRNAs and suppressed the expression of inflammatory cytokines, like JTE-607. These findings indicated that CPSF3 is a direct target of JTE-607 and a new potential target for the treatment of disease-related abnormal cytokine production.

Blonanserin suppresses impulsive action in rats.

High impulsivity will increase the risk of criminal behavior, drug abuse, and suicide. We chose two drugs by following a strategy recently we proposed for identifying potential anti-impulsivity drugs, and examined the effects on impulsive action in rats by using a 3-choice serial reaction time task. We showed that the administration of blonanserin, an atypical antipsychotic, reduced impulsive actions in a U-shaped manner. 1-(2-Pyriidinyl)-piperazine, an active metabolite of buspirone or tandospirone, also slightly reduced impulsive actions, though it impaired motor functions. These results affirm the validity of our strategy, but require its refinement for developing anti-impulsivity drugs.

Superiority of Dynamic Needle Tip Positioning for Ultrasound-Guided Peripheral Venous Catheterization in Patients Younger Than 2 Years Old: A Randomized Controlled Trial.

OBJECTIVES: This study evaluated whether the dynamic needle tip positioning technique increased the success rate of ultrasound-guided peripheral venous catheterization in pediatric patients with a small-diameter vein compared with the static ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PATIENTS: The study population included 60 pediatric patients less than 2 years old who required peripheral venous catheterization in the PICU. INTERVENTIONS: Patients were randomly divided into the dynamic needle tip positioning (n = 30) or static group (n = 30). Each group received ultrasound-guided peripheral venous catheterization with or without dynamic needle tip positioning, respectively. The Fisher exact test, Kaplan-Meier curve plots, log-rank tests, and Mann-Whitney U test were used in the statistical analysis. MEASUREMENTS AND MAIN RESULTS: The first-attempt success rate was higher in the dynamic needle tip positioning group than in the static group (86.7% vs 60%; p = 0.039; relative risk = 1.44; 95% CI, 1.05-2.0). The overall success rate within 10 minutes was higher in the dynamic needle tip positioning group than in the static group (90% vs 63.3%; p = 0.03; relative risk = 1.42; 95% CI, 1.06-1.91). Significantly fewer attempts were made in the dynamic needle tip positioning group than in the static group (median [interquartile range, range] = 1 [1-1, 1-2] vs 1 [1-2, 1-3]; p = 0.013]). The median (interquartile range) catheterization times were 51.5 seconds (43-63 s) and 71.5 seconds (45-600 s) in the dynamic needle tip positioning and static groups, respectively (p = 0.01). CONCLUSIONS: Dynamic needle tip positioning increased the first-attempt and overall success rates of ultrasound-guided peripheral venous catheterization in pediatric patients less than 2 years old.

Dynamic Needle Tip Positioning for Ultrasound-Guided Arterial Catheterization in Infants and Small Children With Deep Arteries: A Randomized Controlled Trial.

OBJECTIVE: Arterial catheterization for infants and small children is technically challenging. This study evaluated whether the dynamic needle tip positioning (DNTP) technique improved the success rate of ultrasound-guided radial artery catheterization in patients with a radial artery depth ≥4 mm compared with the conventional ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PARTICIPANTS: Patients (n = 40; age <3 years) with artery depth ≥4 mm. INTERVENTIONS: Patients were divided randomly into 2 groups. The DNTP group received ultrasound-guided radial artery catheterization with DNTP; the conventional group received catheterization without DNTP. MEASUREMENTS AND MAIN RESULTS: First-attempt success rates were 85% and 50% in the DNTP and conventional groups, respectively (p = 0.018; relative risk = 1.7; 95% CI: 1.06-2.73). Overall success rates within 10 minutes were 95% and 60% in the DNTP and conventional groups, respectively (p = 0.008; relative risk = 1.58; 95% CI: 1.09-2.3). Posterior wall puncture rates were 5% and 50% in the DNTP and conventional groups, respectively (p = 0.0014; relative risk = 0.1; 95% CI: 0.014-0.71). Significantly fewer attempts were made in the DNTP group (median = 1 v 1.5; p = 0.01). The median catheterization times were 38 seconds (34-55.5) and 149 seconds (49.5-600) in the DNTP and conventional groups, respectively (p = 0.0003). CONCLUSION: Dynamic needle tip positioning improved first-attempt and overall success rates of ultrasound-guided radial artery catheterization in pediatric patients with a radial artery depth ≥4 mm.

Motor strategy for rapid gait initiation under conditions of limited center of pressure control.

[Purpose] The general motor strategy for gait initiation is achieved by the difference between the center of gravity and center of pressure; it be as bigger under speed optimization. This study aimed to investigate the motor pattern in rapid gait initiation under conditions of limited backward displacement of center of pressure. [Participants and Methods] The participants were 30 healthy young males (mean age, 19.7 ± 1.0 years). They performed a gait initiation task at three center of pressure start positions (anterior, middle, and posterior) and two speed conditions (normal and rapid). The gait initiation motion was measured using a video camera and motor pattern in the images was classified. The center of pressure position was continuously monitored using a pressure distribution measurement system. [Results] Forward tilt pattern was the most common under no limited center of pressure control and normal speed. The backward tilt pattern was the most preferred in the posterior position under limited center of pressure control and rapid speed. Displacement of the center of pressure showed a significant decline when the center of pressure start position was displaced backward. [Conclusion] The backward tilt pattern is the most effective motor strategy to increase the forward speed of the center of gravity.

Repeated fluvoxamine treatment recovers early postnatal stress-induced hypersociability-like behavior in adult rats.

Childhood maltreatment is associated with impaired adult brain function, particularly in the hippocampus, and is not only a major risk factor for some psychiatric diseases but also affects early social development and social adaptation in later life. The aims of this study were to determine whether early postnatal stress affects social behavior and whether repeated fluvoxamine treatment reverses these changes. Rat pups were exposed to footshock stress during postnatal days 21-25 (at 3 weeks old: 3wFS). During the post-adolescent period (10-14 weeks postnatal), the social interaction test and Golgi-cox staining of dorsal hippocampal pyramidal neurons were performed. Following exposure to footshock stress, 3wFS rats showed an increase in social interaction time, which might be practically synonymous with hypersociability, and a decrease in spine density in the CA3 hippocampal subregion, but not in CA1. These behavioral and morphological changes were both recovered by repeated oral administration of fluvoxamine at a dose of 10 mg/kg/day for 14 days. These findings suggest that the vulnerability of the hippocampal CA3 region is closely related to social impairments induced by physical stress during the juvenile period and shed some light on therapeutic alternatives for early postnatal stress-induced emotional dysfunction.

Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial.

BACKGROUND: In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. OBJECTIVES: To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. DESIGN: Randomised controlled study. SETTING: A tertiary hospital. PATIENTS: Sixty women undergoing breast cancer surgery between April 2014 and February 2015. INTERVENTIONS: The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. MAIN OUTCOME MEASURES: Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. RESULTS: PECS block combined with propofol-remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) µg ml; P < 0.001) but not remifentanil consumption (PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) µg kg h; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]). CONCLUSION: In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013435).

A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models.

Emphysema is a typical component of chronic obstructive pulmonary disease (COPD), a progressive and inflammatory airway disease. However, no effective treatment currently exists. Here, we show that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette smoke-exposed mice. To confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3--6]Galß1-4[SO3--6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and microcomputed tomography analyses revealed that, in the mouse elastase-induced emphysema model, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx, as well as the levels of inflammatory cytokines, tissue-degrading enzymes (matrix metalloproteinases), and myeloperoxidase in bronchoalveolar lavage fluid, suggesting that L4 suppressed inflammation in the lung. L4 consistently blocked the chemotactic migration of neutrophils in vitro. Moreover, in the case of the exacerbation model, L4 inhibited inflammatory cell accumulation to the same extent as that of dexamethasone. Taken together, L4 represents one of the potential glycan-based drugs for the treatment of COPD through its inhibitory action against inflammation.