PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p < 0.05). TPN increased nitrite but did not affect permeability or MMP-2 levels significantly (p > 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.
Adenosine ; Blotting, Western ; Cyclic GMP ; Dipyridamole ; Humans ; Matrix Metalloproteinases ; Nitric Oxide ; Permeability ; Phosphodiesterase Inhibitors ; Theophylline ; Trabecular Meshwork

A debridement method that causes minimal damage to normal tissue during the removal of necrotic tissue is important for chronic wound healing. A new instrument based on low-frequency ultrasound, the Misonix SonicOne O.R. System ® (Bioventus, Farmingdale, NY, USA), creates 22.5 kHz ultrasound waves that cause cavitation or oscillating micro-gas bubbles to debride unhealthy tissue. The device was used for debridement on nine patients with chronic wounds of varying etiology: two patients with decubitus ulcers, one patient with a crush injury, and seven patients with burns. The eschar and unhealthy granulation tissue were removed effectively with no damage to normal skin and soft tissue. No bleeding complications occurred and postoperative analgesics were not required. Compared to surgical debridement, the low-frequency ultrasound device was effective, easy and safe to use, and caused less pain and bleeding. It can be recommended as a treatment method for chronic wounds, comparable to surgical wound debridement.

Background: Scabies, a common contagious skin disease caused by ectoparasites, is a significant public health concern in healthcare facilities, including tertiary hospitals. Objective: This study aimed to assess the clinical characteristics of hospitalized patients who were diagnosed with scabies. We focused on determining whether patient-related factors such as height, weight, underlying diseases, mobility, mental alertness, cognitive impairment, catheter insertion, and the presence of caregivers influenced the failure of the initial diagnosis or treatment. Methods: We retrospectively analyzed the medical records of 81 patients who were diagnosed with scabies during hospitalization between January 2011 and June 2023. Results: Of the 81 patients, 45 (55.6%) were male, with a mean age of 76.5 years. The most common primary diagnosis was an infectious disease (66.7%). The main suspected routes of infection were care facilities (63.5%) for patients who already had pruritic skin lesions before admission, and contact with caregivers (80.0%) for patients who developed new skin lesions after admission. The initial consultation failed to diagnose scabies in 19.8% of the patients, and among those, 62.5% had not undergone initial microscopic examination. Patients who were initially misdiagnosed had significantly longer hospitalizations and scabies treatment durations. Among the patients who underwent follow-up microscopic examination after the initial treatment, 60.0% showed positive results. Overall, 54.2% of the patients experienced initial treatment failure. Patient-related factors did not significantly differ between patients with and without initial diagnostic failure and between patients with and without initial treatment failure. Conclusion Dermatologists should consider performing microscopic examinations more frequently in hospitalized patients to improve diagnostic accuracy. Considering the high treatment failure rate, follow-up microscopic evaluation is recommended after initial treatment.

Objectives: Severe mental illness has become one of the leading concerns for the cost of health services. This study analyzed the demographic characteristics and compared the patterns of medical health service use according to the diagnosis of severe mental illness, including schizophrenia spectrum disease, bipolar disease, and major depressive disorder. Methods: The data from the National Health Insurance Corporation were analyzed, selecting subjects diagnosed at least once for severe mental illness between 2014 and 2019. Severe mental illness included the following: schizophrenia, schizotypal, and delusional disorders (F20– 29); manic episodes and bipolar affective disorder (F30–31); and moderate depressive episodes with psychotic features and recurrent depressive disorder (F32.3–F33). The demographic factors and patterns of medical services, such as outpatient, hospitalization, and re-admission differences, were compared according to the diagnostic categories. Results: This study included 842459 patients, with 39.6% people in F20–F29, 33.7% in F32.3– F33, and 26.8% in the F30–F31 category. There were significant differences in gender, age, insurance type, Charlson Comorbidity Index score, and economic level according to the diagnostic categories. The engagement of medical health services also showed significant differences among the diagnostic categories. F32.3–F33 showed higher engagement of outpatients than the out-groups, while F20–F29 showed a higher admission rate. The hospitalization duration was significantly longer in F20–F29, and the re-admission rate after discharge within one year was significantly higher in the same group. Conclusion This paper reviewed the differences in medical care utilization among severe mental illness. The result emphasizes the need for a mental health care system broadening to the community, facilitating psychosocial intervention, and case management.

The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.
3T3 Cells ; Animals ; *Bifidobacterium ; Body Weight ; Cell Division/physiology ; Cytotoxicity, Immunologic ; Flow Cytometry ; Humans ; Immunophenotyping ; Jurkat Cells ; Killer Cells, Natural/immunology ; *Lactobacillus casei ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental/immunology/*therapy ; Probiotics/*pharmacology ; Survival Analysis ; T-Lymphocytes/immunology

Background: Appropriate platelet transfusion is essential for patient blood management and allocating limited healthcare resources. Therefore, this study evaluated the appropriateness of platelet transfusion in two tertiary hospitals. Methods: At Chonnam National University Hospital (Hospital A) and Chonnam National University Hwasun Hospital (Hospital B), 1,470 platelet transfusions (299 and 1,171 cases at Hospitals A and B, respectively) during a single month were reviewed retrospectively using the Korean Transfusion Guidelines (5th edition). Results: The most common indications were therapeutic transfusion to ensure hemostasis (54.8%) at Hospital A and to prevent spontaneous bleeding in patients with hematologic/oncologic diseases (65.8%) at Hospital B. Overall, 87.3% and 76.3% of transfusions were appropriate at Hospitals A and B, respectively. According to the different transfusion indications, the therapeutic transfusions were appropriate in more than 80% of cases in both hospitals.The appropriateness of prophylactic transfusions against spontaneous bleeding was 80.7% and 69.3%, respectively, and those before surgery or invasive procedures were 72.0% and 66.2%, respectively. Of the 38 and 278 inappropriate transfusions in Hospitals A and B, respectively (as determined by pre-transfusion platelet counts), most cases had platelet counts between 50 and 100×109 /L in Hospital A (23 cases) and between 20 and 50×109 /L in Hospital B (198 cases). Conclusion The two hospitals differed in terms of transfusion indications, appropriateness, and cases of inappropriateness. The indications and appropriateness of platelet transfusion should be reviewed in real practice on a hospital-by-hospital basis to improve transfusion management.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.