Radial dependence diagnosis of inductively coupled Ar plasma based upon optical emission spectroscopic measurement with spectral reflectance compensation.

This study proposed a simple method to evaluate the spectral reflectance of the inner wall of a vacuum chamber. A method for calculating spectral emission coefficients by taking the spectral reflectance of the chamber inner wall into account was proposed. Furthermore, plasma diagnosis based on optical emission spectroscopic (OES) measurement was performed so as to obtain radial dependence of electron temperature Te and density Ne of a radio frequency inductively coupled Argon (Ar) plasma by applying a collisional-radiative model to radially resolved emission spectra of the Ar plasma assuming axial symmetry. In addition, Langmuir probe measurement and electromagnetic simulation were performed and compared with the OES-based plasma diagnosis results. The spectral radiance compensation improved the diagnostic result by 0.6% and 3.1% for Te and Ne, respectively.

A novel BRD4 degrader, ARV-825, attenuates lung fibrosis through senolysis and antifibrotic effect.

BACKGROUND: Recent studies suggest that cellular senescence is related to the pathogenesis of idiopathic pulmonary fibrosis. However, cellular senescence has yet to be targeted therapeutically in clinical practice. ARV825, a recently developed BRD4 degrader, has been reported as a novel senolytic drug. Conversely, it has also been reported that BRD4 regulates the pro-fibrotic gene expression of fibroblasts. Therefore, this study focuses on the senolytic and anti-fibrotic effects of ARV825 and evaluated these effects on lung fibrosis. METHODS: Lung fibroblasts were induced to senescence through serial passage. The expression of senescence markers and pro-fibrotic markers were determined through quantitative PCR or immunoblot analysis. Lung fibrosis was induced in mice through intratracheal administration of bleomycin. Mice treated with ARV825 underwent histological analysis of lung fibrosis using the Ashcroft score. Total lung collagen was quantified through a hydroxyproline assay. Respiratory mechanics analysis was performed using the flexiVent system. RESULTS: For senescent cells, ARV825 induced the expression of an apoptosis marker while reducing the expression of BRD4 and senescence markers. On the other hand, for early passage pre-senescent cells, ARV825 reduced the expression of collagen type 1 and α-smooth muscle actin. In an experimental mouse model of lung fibrosis, ARV825 attenuated lung fibrosis and improved lung function. Immunohistochemical staining revealed a significant decrease in the number of senescent alveolar type 2 cells in lung tissue due to ARV825 treatment. CONCLUSIONS: These results suggest that ARV825 may impact the progressive and irreversible course of fibrotic lung diseases.

A polo-like kinase inhibitor identified by computational repositioning attenuates pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with few effective therapeutic options. Recently, drug repositioning, which involves identifying novel therapeutic potentials for existing drugs, has been popularized as a new approach for the development of novel therapeutic reagents. However, this approach has not yet been fully utilized in the field of pulmonary fibrosis. METHODS: The present study identified novel therapeutic options for pulmonary fibrosis using a systematic computational approach for drug repositioning based on integration of public gene expression signatures of drug and diseases (in silico screening approach). RESULTS: Among the top compounds predicted to be therapeutic for IPF by the in silico approach, we selected BI2536, a polo-like kinase (PLK) 1/2 inhibitor, as a candidate for treating pulmonary fibrosis using an in silico analysis. However, BI2536 accelerated mortality and weight loss rate in an experimental mouse model of pulmonary fibrosis. Because immunofluorescence staining revealed that PLK1 expression was dominant in myofibroblasts while PLK2 expression was dominant in lung epithelial cells, we next focused on the anti-fibrotic effect of the selective PLK1 inhibitor GSK461364. Consequently, GSK461364 attenuated pulmonary fibrosis with acceptable mortality and weight loss in mice. CONCLUSIONS: These findings suggest that targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting lung fibroblast proliferation without affecting lung epithelial cells. In addition, while in silico screening is useful, it is essential to fully determine the biological activities of candidates by wet-lab validation studies.

The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-ß production in regulatory T-cells.

BACKGROUND: Lymphocyte-specific protein tyrosine kinase (Lck) is a member of the Src family of tyrosine kinases. The significance of Lck inhibition in lung fibrosis has not yet been fully elucidated, even though lung fibrosis is commonly preceded by inflammation caused by infiltration of T-cells expressing Lck. In this study, we examined the effect of Lck inhibition in an experimental mouse model of lung fibrosis. We also evaluated the effect of Lck inhibition on the expression of TGF-ß1, an inhibitory cytokine regulating the immune function, in regulatory T-cells (Tregs). METHODS: Lung fibrosis was induced in mice by intratracheal administration of bleomycin. A-770041, a Lck-specific inhibitor, was administrated daily by gavage. Tregs were isolated from the lung using a CD4+CD25+ Regulatory T-cell Isolation Kit. The expression of Tgfb on Tregs was examined by flow cytometry and quantitative polymerase chain reaction. The concentration of TGF-ß in bronchoalveolar lavage fluid (BALF) and cell culture supernatant from Tregs was quantified by an enzyme-linked immunosorbent assay. RESULTS: A-770041 inhibited the phosphorylation of Lck in murine lymphocytes to the same degree as nintedanib. A-770041 attenuated lung fibrosis in bleomycin-treated mice and reduced the concentration of TGF-ß in BALF. A flow-cytometry analysis showed that A-770041 reduced the number of Tregs producing TGF-ß1 in the lung. In isolated Tregs, Lck inhibition by A-770041 decreased the Tgfb mRNA level as well as the concentration of TGF-ß in the supernatant. CONCLUSIONS: These results suggest that Lck inhibition attenuated lung fibrosis by suppressing TGF-ß production in Tregs and support the role of Tregs in the pathogenesis of lung fibrosis.

The Characteristics and Outcomes of Patients Transported by Ambulance Due to Ambulatory Care Sensitive Condition: A Population-Based Descriptive Study in Osaka, Japan.

Background: Ambulatory care sensitive conditions (ACSCs) are defined as clinical conditions for which the risk of emergency hospital admission can be reduced by timely and effective ambulatory care. However, the actual status of patients with ACSCs who are transported by ambulance and their outcomes have not been fully elucidated. The purpose of this study was to reveal characteristics and outcomes of patients with ACSCs who were transported by ambulance using population-based registry data in Osaka, Japan. Methods: This descriptive epidemiological study was conducted in the 5-year period from January 2016 to December 2020, and included patients who were transported by ambulance due to sudden illness. In this study, ACSC was further classified into acute ACSCs, chronic ACSCs, and preventable ACSCs based on the ICD-10. The number of patients transported by ambulance for ACSCs per 100,000 population in each age group was calculated for each year. In addition, Poisson regression models were used to assess the trend in the number of ACSCs patients transported by ambulance. Results: A total of 1,572,152 patients were included in this study (acute ACSCs, n = 69,621; chronic ACSCs, n = 12,250; preventable ACSCs, n = 96,036; and non-ACSCs, n = 1,394,245). The overall median age was 71 years (95% confidence interval [CI], 46-92). Patients with acute ACSCs (median age: 76 years [IQR: 60-84]) and chronic ACSCs (median age: 80 years [IQR: 72-87]) were older, while patients with preventable ACSCs were younger (median age: 66 years [95%CI: 3-81]) and included a high proportion of children (33.3%, 32,002/96,036). Regarding the outcome after treatment at the emergency department, 42.6% (670,392/1,572.152) of patients were hospitalized, while 82.3% (10,079/12,250) of patients with chronic ACSCs were hospitalized. No change was observed in adults (P = 0.001) or elderly (age ≥65 years) individuals (P = 0.376) with preventable ACSCs, however, among children, the number increased until 2019 (732.5) and then decreased in 2020 (371.8) (P = 0.392). Conclusion: In this study, patients with chronic ACSCs were predominantly elderly, while patients with preventable ACSCs were polarized between children and the elderly. Among patients with preventable ACSCs, there was no change over time in adults and children, but there was a marked decrease among the elderly after 2020.

Neuropsychiatric systemic lupus erythematosus with cerebellar vasculitis and obstructive hydrocephalus requiring decompressive craniectomy.

A 36-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE) was admitted to our hospital due to increasing disease SLE activity. Despite the intensification of immunosuppressive treatment, headache newly developed and worsened. Magnetic resonance imaging (MRI) revealed spreading of a high-intensity area along the sulci of the bilateral cerebellar hemispheres. She was diagnosed with neuropsychiatric SLE and methylprednisolone (mPSL) pulse therapy was started. However, consciousness disorder due to cerebellar oedema with obstructive hydrocephalus appeared and required decompressive craniectomy. The histological findings of the biopsy specimens from cerebellar vermis were compatible with features of vasculitis. She was successfully treated adding intravenous cyclophosphamide therapy.

Clinical features of interstitial pneumonia associated with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) commonly affects the lungs. However, the incidence of interstitial pneumonia (IP) related to SLE was reported to be about 10%, less than in the case of other connective tissue diseases, and the mechanism via which IP is related to SLE remains to be elucidated. METHODS: We retrospectively reviewed the medical records and high-resolution computed tomography (HRCT) images of 69 SLE patients who were admitted to our hospital between January 2011 and December 2015. RESULTS: Fifty-five of the patients were female (80%), and the mean age at the onset of SLE was 42.4 years. IP developed in 20 patients (29%), 14 of whom were female (70%), and the mean age at SLE onset was 53.4 years, significantly older than those without IP (38.0 years) (p = 0.003). Half of the patients were found to have IP during the initial diagnosis of SLE. The IP pattern on the HRCT images was consistent with that of usual interstitial pneumonia (UIP) in 25% of the patients and of nonspecific interstitial pneumonia (NSIP) in 55%. One patient exhibited acute exacerbation but survived. The radiological findings revealed that the disease progressed slowly in most of the patients; however, pulmonary function was retained. No significant differences were observed in the survival rates between patients with and without IP. CONCLUSION: In SLE cases, IP primarily occurred in male and elderly patients. In addition to the NSIP pattern, the UIP pattern was evident on HRCT scans of IP-related SLE. The survival of SLE patients was unrelated to IP.

A case of interstitial pneumonia associated with anti-PL-7 antibody in a patient with rheumatoid arthritis.

A 65-year-old female had been treated rheumatoid arthritis (RA), interstitial pneumonia (IP) and nephrotic syndrome with prednisolone and cyclosporine. She was emergently admitted to our hospital due to the worsening exertional dyspnea and severe hypoxemia. Chest computed tomography (CT) showed new diffuse ground-glass opacities (GGOs) with slight consolidations along with bronchovascular bundle were observed in addition to pre-existing reticular shadows in both lungs with lower lobe-predominance. An acute exacerbation (AE) of pre-existing IP triggered by an infection was suspected, and the treatment with antibiotics and corticosteroid pulse therapy improved her general condition and chest radiological findings. Because some auto-antibodies associated with acute/subacute onset IP have recently become available in clinic, we examined those including anti-aminoacyl tRNA synthetase (ARS) antibodies, and found that she was positive for anti-PL-7 antibody. We diagnosed her anti-synthetase syndrome (ASS) without symptom of myositis, and her IP was considered to be ASS-related. The careful consideration is necessary to precisely diagnose and treat the patients with RA-associated interstitial lung diseases as the several etiologies may be overlapped in the same patient. J. Med. Invest. 65:147-150, February, 2018.

[Significance of Allowing Pharmacy Students to Attend Visits to Home Care Patients].

In 2006, with the admission of a new batch of students, pharmaceutical education became a 6-year course. This was a result of the urgent need to train a new generation of pharmacists to respond to increasingly advanced and intricate medical care as well as the specific need to coordinate with multiple occupational categories. Meanwhile, with Japan becoming an aged society, medical care has undergone functional differentiation, and home care is now being promoted. As part of an 11- week practical course for 5th-year practical training, students attended visits to home care patients from an early stage, making it possible for them to be present at multiple visits. This was highly significant because it allowed students to experience various disease states of different patients and increase their practical knowledge of pharmaceuticals. This study explores the case example of proposals made by pharmacy students for improving medication-related problems in home care patients during 5th-year practical training.

A DNA hybridization sensor based on catalytic response by platinum deposition.

We report a novel electrochemical sensing system for single-stranded DNA (ssDNA) with a specific sequence based on the catalytic reduction of protons with platinum deposited by the electrochemical reduction of chloro-2,2':6',2''-terpyridine platinum(II) chloride dihydrate (Pt complex) on a glassy carbon (GC) electrode. There was no catalytic property observed for proton reduction at the GC electrode, while the platinum deposited by the reduction of the Pt complex shows the catalytic activity of proton reduction. The intercalation of the Pt complex with double-stranded DNA (dsDNA) decreased the concentration of the free Pt complex with a concomitant diminution in the electrochemical catalytic current due to steric hindrance and a decrease in the diffusion coefficient of the intercalated Pt complex. Thus, the catalytic current of proton reduction by platinum deposited on a GC electrode decreased with an increase in the concentration of target ssDNA, when capture DNA with a complementary sequence was present in the solution to form the hybrid dsDNA. A detectable concentration range was estimated and found to be 0.1-1.0 µM. The catalytic current was significantly larger than the reduction current of the Pt complex, resulting in the sensitive detection of ssDNA. Furthermore, the present method is simply due to the immobilization of capture DNA being unnecessary.

Effective enzyme saccharification and ethanol production from Japanese cedar using various pretreatment methods.

We investigated an effective method for the pretreatment of Japanese cedar for efficient enzymatic saccharification and ethanol production. A 45-atm steam explosion provided a comparatively large amount of glucose and reducing sugars. Addition of polyethylene glycol (PEG) influenced the digestibility of holocellulose in a 35-atm steam-exploded sample. However, we observed a negative effect on enzymatic saccharification when sodium hydroxide was used in the pretreatment. The maximum values of glucose and reducing sugars produced using consecutive pretreatments with a 25-atm steam explosion and an ionic liquid were 408 and 462 mg/(g initial dry sample), respectively. The most positive effects on the enzymatic saccharification kinetics were observed when the above consecutive pretreatment methods were used. However, using the organosolv treatment of wood chips without the steam explosion is a more cost-effective pretreatment method for the enzymatic saccharification of Japanese cedar, and this results in 386 and 426 mg/(g initial dry sample) of glucose and reducing sugars, respectively.