• Korean journal of dermatology
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• v.56 no.10
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• pp.631-635
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• 2018

Microvenular hemangioma (MVH) is a rare acquired benign vascular neoplasm, which presents commonly as a solitary purple-to-red nodule or plaque measuring approximately 10 mm in diameter. MVH occurs primarily on the extremities or the trunk. Most lesions are solitary, and multiple lesions are rare. Histopathological features of MVH include numerous, scattered, thin and irregularly branching small vessels in the dermis and endothelial cells without atypia. Owing to similarities in clinical morphology and histopathological features, MVH may often be indistinguishable from the early patch stage of Kaposi sarcoma. Immunohistochemical (IHC) analysis helps differentiate between the 2 diseases. The results of IHC tests in patients with MVH show positive staining for CD31 and smooth muscle actin and typically, negative staining for the human herpes virus 8 antigen. We report a rare case of multiple MVH clinically mimicking the early patch stage of Kaposi sarcoma in a 63-year-old woman who presented with a 3-year history of slowly growing, compressible, soft, bluish-purple macules and plaques on the trunk and right arm.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.71-80
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• 2019

Background: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. Methods: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of $M_2$ and $M_3$ receptors were examined. Results: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of ${\alpha}$-smooth muscle actin were attenuated. Tiotropium enhanced the expression of $M_2$ but decreased expression of $M_3$ in all aged groups of OVA. Conclusion: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression $M_3$ and $M_2$ muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.525-532
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• 2021

We have investigated the relative roles of α₁-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α_1A-adrenoceptor antagonist RS100329 (10^-9M-10^-7M) significantly reduced the response to the first pulse, the α_1D-adrenoceptor antagonist BMY7378 (10^-7M-10^-6M) significantly reduced the response to the first two pulses, and the non-selective α₁-adrenoceptor antagonist prazosin (10^-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α_1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α_1D-adrenoceptor and a larger early α_1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α₁-adrenoceptor component is revealed by prazosin to be α_1B-adrenoceptor mediated. α_1B-Adrenoceptor activation probably facilitates contractions mediated by other α₁-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α₁-adrenoceptor blockade, particularly α_1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

• Archives of Plastic Surgery
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• v.48 no.1
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• pp.33-43
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• 2021

Background Acellular dermal matrices (ADMs) have become an essential material for implant-based breast reconstruction. No previous studies have evaluated the effects of sterility of ADM under conditions of radiation. This study compared sterile (irradiated) and aseptic (non-irradiated) ADMs to determine which would better endure radiotherapy. Methods Eighteen male Balb/C mice were assigned to the control group with no irradiation (group 1) or one of two other groups with a radiation intensity of 10 Gy (group 2) or 20 Gy (group 3). Both sterile and aseptic ADMs were inserted into the back of each mouse. The residual volume of the ADM (measured using three-dimensional photography), cell incorporation, α-smooth muscle actin expression, and connective tissue growth factor expression were evaluated. The thickness and CD3 expression of the skin were measured 4 and 8 weeks after radiation. Results In groups 2 and 3, irradiated ADMs had a significantly larger residual volume than the non-irradiated ADMs after 8 weeks (P<0.05). No significant differences were found in cell incorporation and the amount of fibrosis between irradiated and non-irradiated ADMs. The skin was significantly thicker in the non-irradiated ADMs than in the irradiated ADMs in group 3 (P<0.05). CD3 staining showed significantly fewer inflammatory cells in the skin of irradiated ADMs than in non-irradiated ADMs in all three groups after 4 and 8 weeks (P<0.05). Conclusions Under radiation exposure, irradiated ADMs were more durable, with less volume decrease and less deposition of collagen fibers and inflammatory reactions in the skin than in non-irradiated ADMs.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.543-551
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• 2021

Nocardiopsis species produce bioactive compounds, such as antimicrobial and anti-cancer agents and toxins. However, no reports have described their anti-inflammatory and anti-fibrotic effects during nasal polyp (NP) formation. In this study, we investigated whether marine-derived bacterial Nocardiopsis sp. 13G027 exerts anti-inflammatory and anti-fibrotic effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and transforming growth factor (TGF)-β1-induced NP-derived fibroblasts (NPDFs). Nitric oxide (NO) and prostaglandin E₂ (PGE₂) levels were analyzed. Extract from Nocardiopsis sp. 13G027 significantly inhibited the upregulation of NO and PGE₂ in LPS-activated RAW 264.7 macrophages. The expression of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt/PKB) in LPS-induced RAW 264.7 macrophages was evaluated; smooth muscle alpha-actin (α-SMA), collagen type I (Col-1), and fibronectin also phosphorylated small mothers against decapentaplegic (SMAD) 2 and 3 in TGF-β1-stimulated NPDFs. The Nocardiopsis sp. 13G027 extract suppressed the phosphorylation of MAPKs and Akt and the DNA-binding activity of activator protein 1 (AP-1). The expression of pro-fibrotic components such as α-SMA, Col-1, fibronectin, and SMAD2/3 was inhibited in TGF-β1-exposed NPDFs. These findings suggest that Nocardiopsis sp. 13G027 has the potential to treat inflammatory disorders, such as NP formation.

• Journal of Industrial Convergence
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• v.20 no.7
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• pp.131-137
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• 2022

In the study, we endeavored to assess the convergence effect of Silybum marianum-derived silymarin and epidemiologically-correlated alcohol intake on vascular contractility and to determine the mechanism involved. There were few reports addressing the question whether thin or thick filament modulation is included in ethanol and silymarin-induced regulation. We hypothesized that ethanol at a low concentration and silymarin play a role in agonist-dependent regulation of vascular contractility. Denuded arterial muscles of Sprague-Dawley male rats were suspended in organ baths and isometric tensions were transduced and recorded using isometric transducers and an automatic data acquisition system. Interestingly, both silymarin and ethanol didn't encourage silymarin alone-induced inhibition in agonists-induced contraction suggesting that endothelial nitric oxide synthesis might be involved in ethanol or silymarin-induced modulation of vascular contractility and additional pathways besides endothelial nitric oxide synthesis such as ROCK inactivation might be involved in the silymarin-induced modulation of vascular contractility.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.2
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• pp.93-100
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• 2022

Objective: The impact of imatinib, a tyrosine kinase inhibitor, on ovarian follicles and several proteins related to follicular function and apoptosis was investigated in mice. Methods: Saline, cyclophosphamide (Cp; 50 or 75 mg/kg), or imatinib (7.5 or 15 mg/kg) was injected once intraperitoneally into female B6D2F1 mice (18 mice in each group). In multiple ovarian sections, the number of various types of follicles and the proportion of good-quality (G1) follicles were counted. The levels of six proteins (anti-Müllerian hormone [AMH], BCL-xL, BAX, acid sphingomyelinase [A-SMase], caspase-3, and α-smooth muscle actin [α-SMA]) within the whole ovaries were quantified using Western blots. Results: Compared to the saline group, a significant reduction of the primordial follicle count was observed in the group treated with imatinib 7.5 and 15 mg/kg, as well as in the group treated with Cp 75 mg/kg. Administration of Cp significantly decreased the proportion of G1 primordial follicles, but administration of imatinib did not. No differences in the AMH, anti-apoptotic BCLX-L, pro-apoptotic BAX, and A-SMase levels in the ovarian tissues were observed among the five groups. However, caspase-3 and α-SMA levels were significantly higher in the imatinib and Cp groups than in the saline group. Conclusion: The administration of imatinib to mice significantly reduced the primordial follicle count and increased the protein levels of caspase-3 and α-SMA. Our findings suggest that imatinib potentially exerts ovarian toxicity via apoptotic processes, similarly to Cp.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.479-499
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• 2022

The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.397-404
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• 2022

Fesoterodine, an antimuscarinic drug, is widely used to treat overactive bladder syndrome. However, there is little information about its effects on vascular K⁺ channels. In this study, voltage-dependent K⁺ (Kv) channel inhibition by fesoterodine was investigated using the patch-clamp technique in rabbit coronary artery. In whole-cell patches, the addition of fesoterodine to the bath inhibited the Kv currents in a concentration-dependent manner, with an IC₅₀ value of 3.19 ± 0.91 μM and a Hill coefficient of 0.56 ± 0.03. Although the drug did not alter the voltage-dependence of steady-state activation, it shifted the steady-state inactivation curve to a more negative potential, suggesting that fesoterodine affects the voltage-sensor of the Kv channel. Inhibition by fesoterodine was significantly enhanced by repetitive train pulses (1 or 2 Hz). Furthermore, it significantly increased the recovery time constant from inactivation, suggesting that the Kv channel inhibition by fesoterodine is use (state)-dependent. Its inhibitory effect disappeared by pretreatment with a Kv 1.5 inhibitor. However, pretreatment with Kv2.1 or Kv7 inhibitors did not affect the inhibitory effects on Kv channels. Based on these results, we conclude that fesoterodine inhibits vascular Kv channels (mainly the Kv1.5 subtype) in a concentration- and use (state)-dependent manner, independent of muscarinic receptor antagonism.

• Archives of Plastic Surgery
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• v.49 no.2
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• pp.275-284
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• 2022

Background Population aging has led to an increased incidence of pressure ulcers, resulting in a social burden and economic costs. We developed a three-dimensional knitted fabric (3-DKF) with a pressure-reducing function that can be applied topically in the early stages of pressure ulcers to prevent progression. Methods We evaluated the effects of the 3-DKF in a streptozotocin-induced diabetes mellitus pressure ulcer mouse model, and the fabric was preliminarily applied to patients. Twelve-week-old male C57BL/6 mice were used for the animal experiments. In the pressure ulcer mouse model, an ischemia-reperfusion injury was created using a magnet on the dorsa of the mice. Pressure was measured with BodiTrak before and after applying the 3-DKF to 14 patients at risk of sacral pressure ulcers. Results In the 3-DKF-applied mice group, the ulcers were shallower and smaller than those in the control group. Compared with the mice in the control group, the 3-DKF group had lower platelet-derived growth factor-α and neutrophil elastase expression, as parameters related to inflammation, and increased levels of transforming growth factor (TGF)-β1, TGF-β3, proliferating cell nuclear antigen, and α-smooth muscle actin, which are related to growth factors and proliferation. Additionally, typical normal tissue staining patterns were observed in the 3-DKF group. In the preliminary clinical analysis, the average skin pressure was 26.2 mm Hg before applying the 3-DKF, but it decreased to an average of 23.4 mm Hg after 3-DKF application. Conclusion This study demonstrated that the newly developed 3-DKF was effective in preventing pressure ulcers through testing in a pressure ulcer animal model and preliminary clinical application.