Current awareness and use of transthoracic echocardiography in evaluation of valvular heart disease in Kumamoto Prefecture -a report from the Kumamoto cardiovascular echocardiography standardization project.

BACKGROUND: There are few reports on transthoracic echocardiography (TTE) for the evaluation of valvular heart disease in a specific area or region. METHODS AND RESULTS: This cross-sectional questionnaire-based survey was conducted in 2023 in Kumamoto Prefecture, where 106 hospitals provide cardiology services. Ninety-three (88%) of the hospitals completed questionnaires regarding TTE. The severity of low flow/low gradient AS was evaluated by dobutamine stress echocardiography in only 7% of hospitals and exercise stress echocardiography for asymptomatic mitral regurgitation in only 5%. Multivariate logistic regression analysis revealed that participation in remote multi-institutional echocardiographic meetings and use of the Kumamoto Prefecture echocardiographic manual were significantly associated with the use of a multi-window approach (P < 0.05). CONCLUSIONS: In Kumamoto Prefecture, echocardiographic measurements are performed according to the recommendations at a relatively low rate. Dissemination of recommendations through remote meetings and the use of the echocardiographic manual may increase the likelihood of TTE being performed according to the recommendations.

1,5-anhydro-D-fructose induces anti-aging effects on aging-associated brain diseases by increasing 5'-adenosine monophosphate-activated protein kinase activity via the peroxisome proliferator-activated receptor-γ co-activator-1α/brain-derived neurotrophic factor pathway.

5'-Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor that serves as a cellular housekeeper; it also controls energy homeostasis and stress resistance. Thus, correct regulation of this factor can enhance health and survival. AMPK signaling may have a critical role in aging-associated brain diseases. Some in vitro studies have shown that 1,5-anhydro-D-fructose (1,5-AF) induces AMPK activation. In the present study, we experimentally evaluated the effects of 1,5-AF on aging-associated brain diseases in vivo using an animal model of acute ischemic stroke (AIS), stroke-prone spontaneously hypertensive rats (SHRSPs), and the spontaneous senescence-accelerated mouse-prone 8 (SAMP8) model. In the AIS model, intraperitoneal injection of 1,5-AF reduced cerebral infarct volume, neurological deficits, and mortality. In SHRSPs, oral administration of 1,5-AF reduced blood pressure and prolonged survival. In the SAMP8 model, oral administration of 1,5-AF alleviated aging-related decline in motor cognitive function. Although aging reduced the expression levels of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and brain-derived neurotrophic factor (BDNF), we found that 1,5-AF activated AMPK, which led to upregulation of the PGC-1α/BDNF pathway. Our results suggest that 1,5-AF can induce endogenous neurovascular protection, potentially preventing aging-associated brain diseases. Clinical studies are needed to determine whether 1,5-AF can prevent aging-associated brain diseases.

Inverse Versus Normal Behavior of Interactions, Elucidated Based on the Dynamic Nature with QTAIM Dual-Functional Analysis.

In QTAIM dual-functional analysis, Hb(rc) is plotted versus Hb(rc) - Vb(rc)/2 for the interactions, where Hb(rc) and Vb(rc) are the total electron energy densities and potential energy densities, respectively, at the bond critical points (BCPs) on the interactions in question. The plots are analyzed by the polar (R, θ) coordinate representation for the data from the fully optimized structures, while those from the perturbed structures around the fully optimized structures are analyzed by (θp, κp). θp corresponds to the tangent line of the plot, and κp is the curvature; θ and θp are measured from the y-axis and y-direction, respectively. The normal and inverse behavior of interactions is proposed for the cases of θp > θ and θp < θ, respectively. The origin and the mechanism for the behavior are elucidated. Interactions with θp < θ are typically found, although seldom for [F-I-∗-F]-, [MeS-∗-TeMe]2+, [HS-∗-TeH]2+ and CF3SO2N-∗-IMe, where the asterisks emphasize the existence of BCPs in the interactions and where [Cl-Cl-∗-Cl]- and CF3SO2N-∗-BrMe were employed as the reference of θp > θ. The inverse behavior of the interactions is demonstrated to arise when Hb(rc) - Vb(rc)/2 and when the corresponding Gb(rc), the kinetic energy densities at BCPs, does not show normal behavior.

Robotic ankle control can provide appropriate assistance throughout the gait cycle in healthy adults.

Ankle foot orthoses are mainly applied to provide stability in the stance phase and adequate foot clearance in the swing phase; however, they do not sufficiently assist during the entire gait cycle. On the other hand, robotic-controlled orthoses can provide mechanical assistance throughout the phases of the gait cycle. This study investigated the effect of ankle control throughout the gait cycle using an ankle joint walking assistive device under five different robotic assistance conditions: uncontrolled, dorsiflexion, and plantar flexion controlled at high and low speeds in the initial loading phase. Compared with the no-control condition, the plantar flexion condition enhanced knee extension and delayed the timing of ankle dorsiflexion in the stance phase; however, the opposite effect occurred under the dorsiflexion condition. Significant differences in the trailing limb angle and minimum toe clearance were also observed, although the same assistance was applied from the mid-stance phase to the initial swing phase. Ankle assistance in the initial loading phase affected the knee extension and ankle dorsiflexion angle during the stance phase. The smooth weight shift obtained might have a positive effect on lifting the limb during the swing phase. Robotic ankle control may provide appropriate assistance throughout the gait cycle according to individual gait ability.

E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis.

Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8-week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

Intramuscular Coherence of the Lower Flexor Muscles during Robotic Ankle-Assisted Gait.

A close-fitting assisted walking device (RE-Gait) designed to assist ankle movements might be a novel approach for acquiring the forefoot rocker function in the gait cycle. The purpose of the present study was to investigate the effects of using RE-Gait by evaluating the intramuscular coherence (IMC) of the two parts of the tibialis anterior muscles (TA), which could indicate whether a common synaptic drive is present. Seventeen healthy volunteers walked on a treadmill at a comfortable speed before, during, and immediately after 15-minute RE-Gait intervention. After RE-Gait intervention, IMC of the two parts of the TA muscles in the beta frequency band in the initial swing phase was significantly enhanced during RE-Gait intervention. In addition, IMCs in the beta and low-gamma frequency bands were significantly correlated with the enhancement ratio of the step length. These results suggest that robotic ankle plantar flexion and dorsiflexion assistance in the initial swing phase may be effective for improving gait function with enhancement of the functioning of the sensorimotor loop.

Current Awareness and Status of Venous Ultrasonography in Kumamoto Prefecture　- A Report of the Kumamoto Cardiovascular Echocardiography Standardization Project.

Background: There are few reports on the current awareness and status of venous ultrasonography, including the number of specialists who perform this procedure, in a specific regional area in Japan. Methods and Results: This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. Of the 366 medical institutions providing cardiology services in Kumamoto Prefecture, 259 (101 general hospitals, 158 small clinics) responded to our questionnaire. In 2017, 21,773 venous ultrasound tests were performed, 21,101 (97%) of which were performed in hospitals and only 672 (3%) were performed in clinics. Both the number of institutions performing venous ultrasounds and the number of tests performed increased over time. Although 317 medical staff in Kumamoto Prefecture were performing transthoracic echocardiography (TTE) when the questionnaires were collected, only 210 performed venous ultrasounds. Although 91% (61/67) of medical institutions could perform TTE within 30 min, only 77% (53/69) performed venous ultrasounds within 30 min. The number of venous ultrasounds per population×100 was largest in the Kumamoto and Kamimashiki areas (1.67) and smallest in the Kamoto area (0.05). Conclusions: This is the first report to reveal the current awareness and status of venous ultrasonography in a specific region in Japan. There are several problems to be overcome, such as a lack of venous ultrasound specialists and the regional disparity in venous ultrasounds in Kumamoto Prefecture.

Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis.

Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), 14-3-3γ, p-ß-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14-3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1ß, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14-3-3γ/p-ß-catenin Ser37/Bax/caspase-3 pathway.

Intrinsic Dynamic and Static Nature of Halogen Bonding in Neutral Polybromine Clusters, with the Structural Feature Elucidated by QTAIM Dual-Functional Analysis and MO Calculations.

The intrinsic dynamic and static nature of noncovalent Br-∗-Br interactions in neutral polybromine clusters is elucidated for Br4-Br12, applying QTAIM dual-functional analysis (QTAIM-DFA). The asterisk (∗) emphasizes the existence of the bond critical point (BCP) on the interaction in question. Data from the fully optimized structures correspond to the static nature of the interactions. The intrinsic dynamic nature originates from those of the perturbed structures generated using the coordinates derived from the compliance constants for the interactions and the fully optimized structures. The noncovalent Br-∗-Br interactions in the L-shaped clusters of the Cs symmetry are predicted to have the typical hydrogen bond nature without covalency, although the first ones in the sequences have the vdW nature. The L-shaped clusters are stabilized by the n(Br)→σ*(Br-Br) interactions. The compliance constants for the corresponding noncovalent interactions are strongly correlated to the E(2) values based on NBO. Indeed, the MO energies seem not to contribute to stabilizing Br4 (C2h) and Br4 (D2d), but the core potentials stabilize them, relative to the case of 2Br2; this is possibly due to the reduced nuclear-electron distances, on average, for the dimers.

E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model.

Perineural adhesions leading to neuropathy are one of the most undesirable consequences of peripheral nerve surgery. However, there are currently no widely used compounds with anti-adhesive effects in the field of peripheral nerve surgery. E8002 is a novel, anti-adhesive, multi-layer membrane that contains L-ascorbic acid (AA). Here, we investigated the effect and mechanism of E8002 in a rat sciatic nerve adhesion model. A total of 21 rats were used. Six weeks after surgery, macroscopic adhesion scores were significantly lower in the E8002 group (adhesion procedure followed by nerve wrapping with E8002) compared to the E8002 AA(-) group (adhesion procedure followed by nerve wrapping with the E8002 membrane excluding AA) and adhesion group (adhesion procedure but no treatment). Correspondingly, a microscopic examination revealed prominent scar tissue in the E8002 AA(-) and adhesion groups. Furthermore, an in vitro study using human blood samples showed that AA enhanced tissue-type, plasminogen activator-mediated fibrinolysis. Altogether, these results suggest that E8002 may exert an anti-adhesive action via AA and the regulation of fibrinolysis.

Short-term effect of a close-fitting type of walking assistive device on spinal cord reciprocal inhibition.

One of the major problems with walking encountered by patients with spastic hemiplegia is diminished toe clearance due to spasticity of their leg muscles. To improve their walking, a specialized robot assist for ankle movements (RE-Gait) has been utilized. The present study examined the neurophysiological effects whether spinal cord reciprocal Ia inhibition (RI) in the leg was altered by using RE-Gait. Sixteen patients with a clinical diagnosis of stroke were divided into the two groups, RE-Gait walking group (Group R) and normal (controlled) walking group (Group C). In each group, they walked on a flat floor for 15 min with or without RE-Gait. The depression of soleus (Sol) H-reflexes conditioned by common peroneal nerve stimuli with the conditioning-test (C-T) intervals of 1, 2, 3, and 4 ms were assessed before and immediately after each walking session. After the intervention, the LSM (SE) of Sol H-reflex amplitude with 1, 2 and 3 ms C-T interval conditions were significantly decreased in group R (1 ms: 88.15 (4.60), 2 ms: 86.37 (4.60), 3 ms: 89.68 (4.62)) compared to group C (1 ms: 105.57 (4.56), 2 ms: 100.89 (4.58), 3 ms: 107.72 (4.58)) [1 ms: p = 0.012, 2 ms: p = 0.035, 3 ms: p = 0.011]. Walking assistive robot that targets ankle movements might be a new rehabilitation tool for regulating spinal cord excitability.

The inhibition of evoked excitatory postsynaptic potentials produced by ammonium chloride in rat hippocampal CA1 neurons.

The depression of evoked fast excitatory postsynaptic potentials (EPSPs) following superfusion with various concentrations (3 µM-5 mM) of ammonium chloride (NH4Cl) were investigated in rat hippocampal CA1 neurons. The amplitude of the evoked fast EPSPs decreased by NH4Cl in a concentration-dependent manner. The half-maximal inhibitory concentration for the inhibition of evoked fast EPSPs was 198 ± 125 µM (n = 8). The facilitation of a pair of field EPSPs elicited by paired-pulse stimulation (40-ms interval) (paired-pulse facilitation, PPF) was recorded following superfusion with NH4Cl (200 µM and 3 mM). The PPF ratio increased to 180 ± 23% (n = 9) in the presence of 200 µM NH4Cl compared with that in the absence of NH4Cl (142 ± 24%, n = 9). In the presence of 3 mM NH4Cl, the PPF ratio increased to 172 ± 30% (n = 7) compared with that in the absence of NH4Cl (126 ± 13%, n = 7). This implies that NH4Cl suppressed the presynaptic release of glutamate. Exogenous glutamate- or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarization elicited by using pressure application did not reduce following superfusion with 200 µM or 5 mM NH4Cl in the presence of 0.3 µM tetrodotoxin, suggesting that NH4Cl did not affect the postsynaptic glutamate response. Action potentials elicited by rectangular outward current injection from CA3 neurons projecting to CA1 neurons were persistent at 200 µM NH4Cl but disappeared at 5 mM NH4Cl. The abolishment of action potentials in the presence of 5 mM NH4Cl was released by increasing the amplitude of the injection current. These results suggest that NH4Cl depresses evoked fast EPSPs mainly via a presynaptic mechanism at low NH4Cl concentrations, and the failure of action potential propagation through the excitatory nerve may also contribute to the depression of evoked fast EPSPs at high NH4Cl concentrations.

Current Awareness and Status of Transthoracic Echocardiography in Kumamoto Prefecture　- A Report of the Kumamoto Cardiovascular Echocardiography Standardization Project.

Background: There are few reports on current awareness and status of transthoracic echocardiography (TTE), including the actual performance rate according to echocardiographic guidelines, in a specific area or region. Methods and Results: This cross-sectional survey study was conducted in Kumamoto Prefecture from October 2018 to March 2019. There are 366 medical institutions advocating cardiology in Kumamoto Prefecture. Of these, 259 (101 hospitals and 158 clinics) returned questionnaires regarding TTE. In all, 150,570 TTEs were performed in 2017. Of these, 132,771 (88%) were performed in hospitals and 17,799 (12%) were performed in clinics. Physicians performed only 5% of TTEs, whereas sonographers performed 86%. Although the modified Simpson method was performed in 90% of hospitals, 3-dimensional echocardiography was performed in only 2% of hospitals. In addition, the left atrial volume index was not examined in approximately 60% of hospitals, and the mean E/E' ratio was not examined in 80% of hospitals. Multivariable logistic regression analysis revealed that having a Fellow of the Japan Society of Ultrasonic in Medicine was significantly and independently associated with guideline-oriented TTE (odds ratio 9.43; 95% confidence interval 1.22-72.71, P<0.05). Conclusions: The rate of echocardiographic measurements performed according to echocardiographic guidelines is exceptionally low in Kumamoto Prefecture. Sufficient dissemination of echocardiographic guidelines may be important in improving this rate.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Evaluation of the Walking-Emotion Relationship for Applying to an Assistive Walking Device.

In this paper, we aimed to evaluate the relationship between walking and emotion. We utilized the two-dimension (2D) walking condition map and the 2D emotion map to confirm the tendency and correlation. From the results, we defined each walking gait corresponding to each emotional state. To valid use walking-emotion relationship, we proposed to use it as a new evaluation method combined with the assistive walking device. Thus, the patient can acquire an improved rehabilitation effect while using the assistive walking device. To significantly use this method, we suggested that the patient walks by following the personal walking limitation region. Therefore, they can control the emotion via the proposed evaluation method. By connecting two maps, the interaction maps were proposed. Finally, the proposed evaluation results can provide a valuable application for various assistive devices to maintain the motivation of the user while performing the rehabilitation. Two-way control (emotion controls walking and walking controls emotion) would be applied to the assistive walking device in future works.

Uric acid enhances alteplase-mediated thrombolysis as an antioxidant.

Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 92% lower in the UA-alteplase-treated group compared with the alteplase-treated group. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA-alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model.

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin⁻eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.

Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombolysis.

The combination of alteplase, a recombinant tissue plasminogen activator, and edaravone, an antioxidant, reportedly enhances recanalization after acute ischemic stroke. We examined the influence of edaravone on the thrombolytic efficacy of alteplase by measuring thrombolysis using a newly developed microchip-based flow-chamber assay. Rat models of embolic cerebral ischemia were treated with either alteplase or alteplase-edaravone combination therapy. The combination therapy significantly reduced the infarct volume and improved neurological deficits. Human blood samples from healthy volunteers were exposed to edaravone, alteplase, or a combination of alteplase and edaravone or hydrogen peroxide. Whole blood was perfused over a collagen- and thromboplastin-coated microchip; capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 69.9% lower in the edaravone-alteplase- than alteplase-treated group. The thrombolytic effect of alteplase was significantly attenuated in the presence of hydrogen peroxide, suggesting that oxidative stress might hinder thrombolysis. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, edaravone significantly inhibited the decrease. Edaravone enhances alteplase-mediated thrombolysis, likely by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

Pleuritis Caused by Mycobacterium kyorinense without Pulmonary Involvement.

We herein describe the first known case of pleuritis caused by Mycobacterium kyorinense without pulmonary involvement. A 48-year-old man undergoing immunosuppressant therapy presented with cough and dyspnea. An accumulation of pleural fluid was noted; however, computed tomography revealed no pulmonary lesions. Cultures of the fluid yielded non-tuberculous mycobacteria, which was identified as Mycobacterium kyorinense. The patient recovered after 6 months of therapy with clarithromycin and moxifloxacin. Clinicians should be aware that Mycobacterium kyorinense can cause pleuritis without pulmonary involvement. When mycobacterial species are isolated from the pleural fluid, precise identification and drug susceptibility testing are warranted.

Activation of cathepsin L contributes to the irreversible depolarization induced by oxygen and glucose deprivation in rat hippocampal CA1 neurons.

Oxygen and glucose deprivation (OGD) elicits a rapid and irreversible depolarization with a latency of ∼5min in intracellular recordings of hippocampal CA1 neurons in rat slice preparations. In the present study, we examined the role of cathepsin L in the OGD-induced depolarization. OGD-induced depolarizations were irreversible as no recovery of membrane potential was observed. The membrane potential reached 0mV when oxygen and glucose were reintroduced immediately after the onset of the OGD-induced rapid depolarization. The OGD-induced depolarizations became reversible when the slice preparations were pre-incubated with cathepsin L inhibitors (types I and IV at 0.3-2nM and 0.3-30nM, respectively). Moreover, pre-incubation with these cathepsin inhibitors prevented the morphological changes, including swelling of the cell soma and fragmentation of dendrites, observed in control neurons after OGD. These findings suggest that the activation of cathepsin L contributes to the irreversible depolarization produced by OGD.