• 한국임상수의학회지
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• 제28권1호
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• pp.63-70
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• 2011

To consider the iliac fossa as the vascular anastomosis site of kidney transplantation for the short-term study of acute rejection in pigs. Twelve domestic pigs weighing 39~48 kg underwent heterotopic renal allgraft transplantation. The experimental animals were divided into 2 groups in terms of renal vascular anastomosis site; the external iliac artery and vein were used in iliac fossa model (n = 6), the abdominal aorta and the caudal vena cava inferior to the kidney were used in abdominal cavity model (n = 6). Renal function was evaluated by daily measurement of plasma creatinine and BUN concentrations. The experiments' health including postoperative complications was also assessed daily for 8 days after transplantation. After euthanazation gross and histopathologic analysis was performed. All six pigs in iliac fossa model developed neuropraxia and lameness of the ipsilateral pelvic limb. However, no necrosis was observed in any pigs. In the abdominal cavity model, durations of both the surgical operation and the vascular anastomosis were significantly longer than those in the iliac fossa model. Furthermore, ischemia injury of the transplanted kidney was increased in abdominal cavity model, which induced accelerated-acute immune response from day 4 after transplantation. Despite of pelvic limb complication, the iliac fossa model showed more advantages including not only less ischemia time related to easy vascular anastomosis, but also less immune response during the acute rejection period. The results indicate that the iliac fossa model may be appropriate to the study of acute rejection in porcine kidney transplantation.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.287-298
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• 2020

Ca²⁺ signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca²⁺ signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca²⁺ concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K⁺ efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca²⁺ influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca²⁺-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca²⁺-sensitive K⁺ channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca²⁺ signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca²⁺ dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.539-545
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• 2016

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

• 대한한의학회지
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• 제21권4호
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• pp.193-203
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• 2000

Objectives : Hindered barrier function of vascular endothelium has been implicated in the initiation and progression of degenerative vascular diseases such as atherosclerosis. In this study, the effect of Sunghyangchungisan(SHCS) as a protectant against oxidant-induced destruction of endothelial barrier function was assessed. Methods : Toward this end, endothelial cells derived from the human umbilical vein were cultured as monolayers on permeable membrane filters. Endothelial permeability was monitored by measuring transendothelial electrical resistance and movement of low density lipoprotein (LDL) across the endothelial monolayer. Results : Along with increased movement of LDL, $H_2O_2$-induced increase in endothelial permeability was paralleled by a decrease in transendotheliaI electrical resistance. The effect of $H_2O_2$ was mimicked by phorbol 12-myristate 13-acetate (PMA), a potent activator of proteinkinase C. Calphostin-C, a protein kinase C inhibitor, effectively blocked the increase in endothelial permeability induced by $H_2O_2$ or PMA, indicating that activation of protein kinase C is associated with the $H_2O_2-induced$ permeability change. SHCS effectively protected the endothelial monolayer against $H_2O_2-induced$ increase in permeability, whereas, it did not affect PMA-induced change. Forskolin, a potent activator of adenylyl cyclase, antagonized $H_2O_2$ to increase endothelial permeability. In addition, in ${H_2O_2}-treated$ cens, intracenular cAMP concentration was significantly decreased, indicating that impaired cAMP production as well as activation of proteinkinase C is a mechanism underlying ${H_2O_2}>-induced$$H_2O_2$ with regard to its effect on intracellular cAMP content. However, SHCS itself did not affect resting cAMP concentration in endothelial cells. Conclusions : These results suggest that SHCS might operate as an effective protectant against oxidant-induced destruction of endothelial barrier function. The mechanism does not appear to involve direct interaction with protein kinase C- or cAMP-associated signaling mechanism.

• Molecules and Cells
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• 제38권3호
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• pp.273-278
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• 2015

The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

• Journal of Cardiovascular Imaging
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• 제31권2호
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• pp.98-104
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• 2023

BACKGROUND: We aimed to investigate left ventricular (LV) global longitudinal strain (GLS) in end-stage renal disease patients and its change after kidney transplantation (KT). METHODS: We retrospectively reviewed patients who underwent KT between 2007 and 2018 at two tertiary centers. We analyzed 488 patients (median age, 53 years; 58% male) who had obtained echocardiography both before and within 3 years after KT. Conventional echocardiography and LV GLS assessed by two-dimensional speckle-tracking echocardiography were comprehensively analyzed. Patients were classified into three groups according to the absolute value of pre-KT LV GLS (|LV GLS|). We compared longitudinal changes of cardiac structure and function according to pre-KT |LV GLS|. RESULTS: Correlation between pre-KT LV EF and |LV GLS| were statistically significant, but the constant was not high (r = 0.292, p < 0.001). |LV GLS| was widely distributed at corresponding LV EF, especially when the LV EF was > 50%. Patients with severely impaired pre-KT |LV GLS| had significantly larger LV dimension, LV mass index, left atrial volume index, and E/e' and lower LV EF, compared to mildly and moderately reduced pre-KT |LV GLS|. After KT, the LV EF, LV mass index, and |LV GLS| were significantly improved in three groups. Patients with severely impaired pre-KT |LV GLS| showed the most prominent improvement of LV EF and |LV GLS| after KT, compared to other groups. CONCLUSIONS: Improvements in LV structure and function after KT were observed in patients throughout the full spectrum of pre-KT |LV GLS|.

• 대한기관식도과학회지
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• 제5권2호
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• pp.174-181
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• 1999

The palatine tonsils(tonsils) and pharyngeal tonsils(adenoids) are situated at the entrance of the respiratory and alimentary tracts and represent the first site of contact with a variety of microorganisms and other antigens present in food and inhaled air. They are known as lymphoid organs carrying out the function of cellular and humoral immunity, and so they form a local protective barrier. And the expression of the vascular endothelial adhesion molecules is known to play an important role for the inflammatory reaction in tonsils and adenoids as well as in other inflammatory tissues, by binding with the receptors on the surface of leukocytes. But although several scientific hypotheses on the role of these lympoid tissues have been suggested, their complete functions have remained unknown. The purpose of this study is to present an basic data of the knowledge on the immunologic physiology of the tonsils and adenoids and their role as active immunologic organs that reinforce the mucosal immunity of the entire upper aerodigestive tract. We examined 16 human tonsils and adenoids and the expression of three endothelial adhesion molecules, vascular endothelial adhesion molecule-1(VCAM-1), intracellular adhesion molecule-1(ICAM-1), and E-selection, in tissue sections using immunohistochemistry. We used the inferior turbinate mucosa obtained from 9 patients getting septal surgery as a control group. The expressions of vascular endothelial adhesion molecule-1(VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) were significantly higher in the tonsils and adenoids. But respectively, there were no significant differences between the tonsils and adenoids. The expression of E-selection was significant higher in the tonsils, but not in the adenoids. We observed that tonsils and adenoids showed significantly higher expressions of vascular endothelial adhesion molecule-1(VCAM-1), intracellular adhesion molecule-1(ICAM-1), and E-selection (in the case of E-selection, only in the tonsils). We propose that these adhesion molecules play an important role for the immunologic reaction by the transendothelial migration of lymphocytes and binding with the receptors on the surface of leukocytes.

• Archives of Reconstructive Microsurgery
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• 제11권1호
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• pp.11-18
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• 2002

Large soft tissue defects around the knee joint are known to significantly diminish joint function. Severe soft tissue defects on the anterior aspect of the knee joint especially bring on significant joint motion limitation. Although simple split skin grafts can cover the skin defect, the progressing scar contracture of the grafted skin causes joint stiffness. One of the best solutions of large soft tissue defects around the knee joint is covering the defect with a good quality skin flap. Separated flaps with one vascular pedicle are good candidates for covering anterior and posterior aspects of the joint for example. Authors performed 12 cases of combined scapular and latissimus dorsi free flaps from 1984 to 2000. Among them, we experienced 5 cases of knee joint defect covering using the double free flap for coverage of the soft tissue defect with preservation of the knee joint function and satisfactory results. The system of flaps based on the subscapular artery and vein provides a variety of composite free flaps. The possible flaps that can be harvested based on this single vascular pedicle include the scapular and parascapular skin flap, the serratus anterior and latissimus dorsi muscular flap, the lateral scapular bone flap, the latissimus dorsi-rib flap, and the serratus anterior-rib flap. This combined flap is available for multiple tissue defects or complex defects because it can be incorporated with skin, muscle and bone flaps. A main advantage is the independent vascular pedicles of each component, which allow freedom in orientation of each components. Consequently it can be freely applied to any form of three dimensional defects on the upper and lower extremities. The combination of scapular cutaneous flap and latissimus dorsi musculocutaneous flap can be resurfaced for massive cutaneous defects on the extremities. We report the use of the combined scapular and latissimus dorsi free flap in five patients to reconstruct massive defects on the extremities with resultant improved joint function. There was no flap failure and minimal complications and disadvantages. The anatomy of this flap is reviewed and the indication and advantages are discussed. All of the five flaps survived and there was no scar contracture affecting the joint motion.

• 대한한방소아과학회지
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• 제12권1호
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• pp.231-256
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• 1998

Experimental studies were done to research the clinical effects of Chihyosan and Chihyosangamibang on the Anti-allergic effect and pulmonary function of $O_3$ intoxicated Rats. Anti-allergic effect experiment consisted of vascular permeability responses to intradermal histamine and serotonin, 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, and delayed type hypersensitivity responses to Picryl Chloride and SRBC. Pulmonary function of $O_3$ intoxicated Rats experiment consisted of lung TBA value, water Contents of the lung, oxygen consumption time, and arterial blood $pCO_2,\;pO_2,\;HCO_3^-$, pH level. The results obtained as follows; 1. In the effects of Chihyosan and Chihyosangamibang on vascular permeability responses to intradermal histamine, both of chihyosan and Chihyosangamibang group revealed significant effect. 2. In the effects of Chihyosan and Chihyosangamibang on vascular permeability responses to intradermal serotonin, both of chihyosan and Chihyosangamibang group revealed significant effect. 3. In the 48hrs homologous passive cutaneous anaphylaxis provoked by the IgE-like antibody against egg white albumin, Chihyosan groups revealed significant effect, but Chihyosangamibang groups revealed none significant effect. 4. In the delayed type hypersensitivity responses to Picryl Chloride, Chihyosan and Chihyosangamibang groups revealed none significant effect. 5. In the delayed type hypersensitivity responses to. SRBC, Chihyosan revealed none significant effect, but Chihyosankamibang revealed significant effect. 6. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of the lung TBA value of lung. 7. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of the water contents of right and left lung. 8. Both of Chihyosan and Chihyosangamibang groups revealed significant effect on decrease of oxygen consumption time. 9. In the decrease effect of arterial blood $pCO_2$ level, both of Chihyosan and Chihyosangamibang groups revealed none significant effect. 10. In the increase effect of arterial blood $pO_2$ level, both of Chihyosan and Chihyosangamibang groups revealed none significant effect. 1. In the decrease effect of arterial blood $HCO_3^-$ level, both of Chihyosan and Chihyosangamibang groups revealed significant effect. 12. In the increase of arterial blood pH level, Chihyosangamibang groups revealed none significant effect, but Chihyosan groups revealed significant effect. According to above stated results, both of Chihyosan and Chihyosangamibang are very usefully for treatment of cough, asthma, chronic obstructive pulmonary diseases and allergic pulmonary diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.203-213
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• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.