T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.

A focus on extracellular Ca²⁺ entry into skeletal muscle

The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca²⁺ in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca²⁺ level is mainly determined by Ca²⁺ movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca²⁺ entry from extracellular spaces to the cytosol has gained significant attention over the past decade. Store-operated Ca²⁺ entry with a low amplitude and relatively slow kinetics is a main extracellular Ca²⁺ entryway into skeletal muscle. Herein, recent studies on extracellular Ca²⁺ entry into skeletal muscle are reviewed along with descriptions of the proteins that are related to extracellular Ca²⁺ entry and their influences on skeletal muscle function and disease.

The maintenance ability and Ca²⁺ availability of skeletal muscle are enhanced by sildenafil

Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca2+ imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. In skeletal myotubes, sildenafil enhanced the activity of ryanodine receptor 1, an internal Ca2+ channel, and Ca2+ movement that promotes skeletal muscle contraction, possibly due to an increase in the resting cytosolic Ca2+ level and a unique microscopic shape in the myotube membranes. Therefore, these results suggest that the maintenance ability of skeletal muscle mass and the contractility of skeletal muscle could be improved by sildenafil by enhancing the proliferation of skeletal myoblasts and increasing the Ca2+ availability of skeletal myotubes, respectively.

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.

Vascular Imaging Using Confocal Microscopy

No abstract available.

TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

The role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the lead (Pb)-induced cellular response was investigated in the cultured endothelial cells. Pb caused progressive cellular death in endothelial cells, which occurred in a concentration- and time-dependent manner. However, Ref-1 overexpression with AdRef-1 significantly inhibited Pb-induced cell death in the endothelial cells. Also the overexpression of Ref-1 significantly suppressed Pb-induced superoxide and hydrogen peroxide elevation in the endothelial cells. Pb exposure induced the downregulation of catalase, it was inhibited by the Ref-1 overexpression in the endothelial cells. Taken together, our data suggests that the overexpression of Ref-1 inhibited Pb-induced cell death via the upregulation of catalase in the cultured endothelial cells.

Massive Perivillous Fibrin Deposition in Placenta

Massive perivillous fibrin deposition (MFD) is a rare condition characterized by heavy accumulation of fibrin in intervillous or perivillous spaces encasing villi throughout the placenta. This condition may cause varying degrees of placental insufficiency, leading to a significantly increased risk of intrauterine growth retardation, intrauterine death, and pre-term delivery. However, the objective criteria for the diagnosis of MFD have not been clearly established. We report a case of MFD associated with intrauterine growth retardation and preterm premature rupture of membranes.

Blockade of airway inflammation and hyper-responsiveness by an angiopoietin-1 variant, COMP-Ang1

Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage. Recently, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 receptor in lung endothelial cells. We have used a mouse model for allergic airway disease to determine effects of COMP-Ang1 on allergen-induced bronchial inflammation and airway hyper-responsiveness. These mice develop the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased levels of Th2 cell cytokines (IL-4, IL-5, and IL-13), adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and chemokines (eotaxin and RANTES), and increased vascular permeability. Intravenous administration of COMP-Ang1 reduced bronchial inflammation and airway hyper-responsiveness. In addition, the increased plasma extravasation in allergic airway disease was significantly reduced by the administration of COMP-Ang1. These results suggest that COMP-Ang1 attenuates airway inflammation and hyper-responsiveness, prevents vascular leakage, and may be used as a therapeutic agent in allergic airway disease.

Partial rescue of the Na+-Ca2+ exchanger (NCX1) knock-out mouse by transgenic expression of NCX1

The null mutation of cardiac Na+-Ca2+ exchanger (NCX1) gene in mice caused death of embryo in utero at embryonic day (ED) 9.0-9.5 and this embryonic lethality appears resulted from abnormal heart development. In the present study, we investigated whether transgenic re-expression of NCX1 in mutant cardiac myocytes could rescue these lethal defects. Transgenic mice expressing the canine NCX1 in a cardiac specific manner were bred into the NCX1 knock-out background but did not prevent the fetal lethality associated with the NCX1 null allele. However, the NCX1 knock-out embryos with an NCX1 transgene survived with heart beatings until ED 10.5 which was one day longer than the survival of the NCX1 knock-out embryos (ED 9.5). At ED 10.5, however, the partially rescued NCX1 embryos might have succumbed to the lack of an organized vasculature in the yolk sacs. The placental labyrinth layer was reduced in size and largely avascular. The transgenic re-expression of NCX1 rescued heart beatings and survived longer, but was still insufficient for the mice to be completely rescued. Importantly, NCX1 was observed to express in the yolk sac and the placenta of wild type mice. The results suggest that defects in extra-embryonic compartments are causal to the lethality, and that NCX1 may play an important role in establishing vascularization in extra-embryonic tissues.

Corrective Rhinoplasty Through the Correction of Combined Deformities / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Recently, the demand for corrective rhinoplasty has increased due to a higher frequency of accidents as well as improved socioeconomic status. Thus, there is an increased interest in the correction of deviated noses in the otorhinolaryngologic field. This study offers a clinical analysis of our experiences in the corrective rhinoplasty and makes a case that the simultaneous correction method by the exteral approach is suitable for combined deformities of the nose. MATERIALS AND METHODS: A retrospective study was performed on 69 patients who underwent corrective rhinoplasty during the last four years. Initially, patients were put under general anesthesia, and the procedures were performed through the external approach. Following the initial corrective rhinoplasty was a simultaneous correction of combined deformities of the nose such as deviated noses with saddle deformity or hump nose or camouflage of the deviation with one or two straight layered cartilage on the nasal dorsum. RESULTS: Satisfactory results were achieved in most cases except in the two cases of incomplete correction, one case of cosmetical unsatisfaction and one case of intermittent nasal obstruction. CONCLUSION: Deviated noses frequently have combined deformities. For better results, it is necessary to correct combined deformities simultaneously. The authors obtained satisfactory results through simultaneous correction of complicated deformities using the external approach.

Reduction Rhinoplasty Using Augmentation of Nasal Tip and Nasion / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A successful reduction rhinoplasty would require more than a hump removal, since most of the patients show drooped nasal tips with an acute naso-frontal angle. For better results, therefore, the patients also need to receive a stronger cephalic rotation of the nasal tip as well as augmentation of the nasion. In order to perform such combined procedures, the external rhinoplasty approach is considered to be suitable for correcting hump noses since this approach provides a better visual field. This report analyses reduction rhinoplasty using augmentation of nasal tip and nasion. MATERIALS AND METHODS: A retrospective study was performed on 46 patients who underwent reduction rhinoplasty from Jan 1994 through May 1997. Almost all of the cases were performed by using the external approach. RESULTS: Reduction rhinoplasty using the external approach of tip projection and augmentation of the nasion following the hump removal gave satisfactory results. CONCLUSION: We conclude that the external approach of augmentation of the nasal tip and the nasion offers satisfactory outcome in reduction rhinoplasty.

Local Production of IgE in Nasal Polyp

Among the several possible etiologic factors for the development of nasal polyp, localized nasal allergy had been insisted to be one of the major factors. This study aims to explore the existence of local production of IgE within nasal polyp, which can be the indirect evidence of localized nasal allergy. Fifty-two patients, who underwent nasal polypectomies between April 1993 and December 1995, were selected. The levels of total IgE and specific IgE of serum and polyp fluids were assessed. By using Donovan's equation, the percentage of local production of IgE in nasal polyp were calculated. Local production of total IgE was demonstrated in 18 cases of 28 polyp patient group (64.3%). Local production of specific IgE for Dermatophagoides pteronyssinus and Dermatophagoides farinae were demonstrated in 6 cases of 24 polyp patient group (25%). These results suggest the existence of local production of IgE in nasal polyp.

Effects of Volume of the Anesthetic Solution and Patient Position / 대한마취과학회지

Factors which may influence the extent of spinal anesthesia include gravity, baricity, volume, doee and concentration of the injected local anesthetic solution, and patient position. We have often experienced unexpected high level of spinal anesthesia and incomplete muscle relaxation when 0.1% tetracaine mixed in distilled water was injected intradurally for the perianal operation in jack-knife position as hypobaric technique. We have done this study to see whether injected volume or patient position influence the level for the perianal surgery. Fourty-eight patients were divided into two groups, group I, 0.1% tetracaine 5 ml, n=24, and group 11, 0.4% tetracaine 1.25 ml, n=24 in the jack-knife position of which cephalad downward angle was 15 degree, 18degree and 23degree. Sensory dermatomal levels of anesthesia were assesed using loss of pinprick aensation at 5 min and 30 min following completion of injection. Results are as follows: 1) Tetracaine mixtures of both groups were consistently hypobaric compared to patient CSF. 2) In both groups, there were significant differences in the sensory block level between 15degree and 18degree and 15degree and 23degree position but no difference between 18degree and 23degree position after 30 min. 3) Level of anesthesia were higher after 30 min than 5 min in the both groups. 4) The effect of volume of injected anesthetic solution could not be seen in the bath groups.

Effects of Needle Size and Needle Bevel Direction on the Postspinal Headache / 대한마취과학회지

The incidence of postspinal headache is one of the well known complications of spinal anesthesia. Several factors such as needle size, bevel direction, multiple dural puncture and previous history of postspinal headache were thought to influence the incidence of postspinal headache. This studies were done to see the effect of needle size (22 and 25 gauge needle) and needle bevel direction (parallel, vertical, oblique insertion to the longitudinal dural fiber) on the incidence, duration, severity and location of spinal headache in the 548 patients underwent spinal anesthesia. The following results wre observed: 1) Neither needle size nor needle bevel direction had effect on the incidence of severity, duration and location of postspinal headache. 2) The ineidence of headache was 8.8% (48 cases), 3) The onset of headache was 1~2 day (67%) and duration of headache was 4~5 day (85%) in postanesthetic day. 4) The severity of headache was mild and moderate in 77% cases. 5) In the half cases, headache was relieved by means of bed rest alone.

SARACAP Monitoring of Anesthesia Machines during Anesthesia / 대한마취과학회지

With recent rise in medico-legal problems, there is also an increase in number of problems involved with anesthesia. Major causes of anesthetic accident are malfunctioning anesthetic machine and inappropriate gas flow and concentration of anesthetic gas, resulting from malfunctioning ventilatory circuit. Therefore, anesthesiologist needs an apparatus to determine the appropriateness of ventilation and a monitoring system to measure a concentration of inspired O2 and inhalation anesthetics. To prevent circulatory and respiratory abnormalities and to promote the safty during anesthesia, we used the SARA monitoring system, as an indicator of safty measure. We monitored the anesthesia machines (n=17), using in operating room in Shinchon Severance hospital, by using the SARA monitoring system which was connected to the distal portion of endotracheal tube. We intended to analysis the relationships between anesthetic machines, vaporizers, ventilators and parameters measured form each machine, in clinical use. The results were as follows; 1) Average used year of anesthesia machines was 7.7 years, that of vaporizers was 7.6 years and that of ventilator's was 4.0 years. 2) When vaporizers dial was fixed at enflurane 2.0%, average measured-FiEnf was 2.02+/-0.22%, equal to dial setting and average FiEnf was 1.70+/-0.25%, usually lower than dial setting. 3) In some anesthesia machines, CO2 rebreathing occured always during ansthesia and FiEnf & FeEnf were decreased in case of CO2 rebreathing. 4) FiEnf by vaporizers was decreased as following orders, Draeger, Ohio and Cyprene.

Effect of Diabetes in the Human on the Metabolism of Enflurane / 대한마취과학회지

Enflurane is metabolized in the liver by the hepatic microsomal enzyme system, cytochrome P-450 (P450IIE1) and induces enzyme system during enflurane exposure. Enhanced biotransformation might occur after enflrane itself and pathologic conditions, such as fasting, diabetes, chemical diabetes. Increased inorganic fluoride, one of the enflurane metabolites could impair renal function. The possibility of increased enflurane defluorination in the diabetic patient, group 1 (control, n= 6), group 2 (blood sugar level below 200mg%, n=6) and group 3 (blood sugar level above 200 mg%, n=5), was investigated by measuring the serum and urine F in the preoperative period and 1 MAC-hr, 2 MAC-hr, immediate postoperative and 24th postoprative hour. In the preoperative, iaunediate postoperative and 24th postoperative hour, the changes of renal function were measured by the BUN and creatinine. The results were as follows: 1) In the diabetic groups, serum fluoride ion increased significantly after enflumane anesthesia at a11 time intervals. Between control and group 3, there were significant difference of aerum inorganic fiuoride after enflurane anesthesia. 2) Urine fluoride levels increased significantly after enflurane anesthesia in all groups 3) There were no changes in renal function after enflurane anestheaia. Our study indicated that enflurane dose not harm diabetic patients.

Effect of Enflurane Anesthesia on Patients Treated with Isoniazid / 대한마취과학회지

Enflurane is metabolized in the liver by the hepatic microsomal enzyme system, cytochrome P-450 and induces enzyme during the enflurane exposure. Enhanced biotransformation might occur after enflurane itself and several other drugs, isoniazid (INH), ethanol and cholorpromazine. Increased inorganic fluroide, one of the enflurane metaboites, could impair renal function. The possibility of increased enflurane defluorination follwing treatment with isoniazid, isoniazid group (n=10) and control group (n= 11) was investigated by the measuring the serum and urine F in the preoperative period and 2 hrs after anesthesia, immediate postoperative and 24th postoperative hour. According to the serum inorganic fluoride concentration, the isoniazid group was divided again into INH high F- and INH low F- groups. In the preoperative, immediate postoperative period and 24th postoperative hour, the changes of renal function were measured by the BUN and creatinine and liver function was measured by the SGOT and SGPT. The results were as follows: 1) Serum inorganic fluoride increased in enflurane anesthesia significantly in all three groups and decreased in the 24th postoperative hour. Among the three groups, enhanced defluorination was the highest in the INH high F group. 2) Urine inorganic fluoride was increased in the control and INH high F group. 3) There were no changes in renal and hepatic function after enflurane anesthesia. Our study indicated that enflurane does not harm the INH treated patient.

High Frequency Jet Ventilation in Tracheal Tumor Surgery / 대한마취과학회지

A 38-year old male patient underwent tracheal reconstruction because of a tracheal tumor. A CT scan showed that the mass was located 5 cm above the carina, the size was 2x1.5cm, and there was a 50% narrowing of the stenotic segment. After endotracheal intubation (1.D. 8mm), a pediatric suction catheter (lenght:40cm, diameter: 2mm) was inserted with a stylet at the side of the tube to pass the stenotic segment with fiberoptic bronchoscopic guidance. Conventional ventilation with an inhalation agent was performed and HFJV was started just prior to the tracheal incision. A driving gas pressure of 1 kg/cm, respiratory rate of 120/min., I:E ratio fo 1:1, and Fio2 of 1.0 were applied through the suction catheter. Ten minutes after HFJV, PaCO2showed 50mmHg. Hypercabia was relieved by increasing the driving gas pressure from 1kg/cm(2) to 1.5 kg/cm(2). HFJV was performed for one and a half hours. During the procedure, blood gas analyses were perfomed frequently and all results revealed an adequate ventilatory status. After completing the end to end anastomosis, conventional ventilation was started until surgery was ended. The patient's course proceeded uneventfully and he was discharged 13 days after surgery.

clinical Application of Pediatric Caudal Anesthesia / 대한마취과학회지

Although regional anesthesia has many advantages over general anesthesia it is not so popular in pediatric patient because of (1) anatomic difference with that of adult (2) lack of patient cooperation (3) difficulty for determination of local anesthetic amount. Among many kinds of regional anesthesia caudal anesthesia is simple, high success rate and needless patient's cooperation with lesser complications. We tried caudal anesthesia in 103 patients from birth to 10 years old children for operation below the inguinal region. We injected 1% lidocaine 10 mg/kg or less for short procedure and 1% lidocaine with 0.5% bupivacaine with 1:1 mixture at the same volume with that of 1% lidocaine only. Thr results were as follows: 1) Pediatric caudal anesthesia is simple and easy with high success rate (more than 93%). 2) There was one case of systemic onvulsion after lidocaine injection and it seemed to be due to multiple blood aspiration during caudal puncture rather than lidocaine overdose. 3) Four children revealedbradycardia below 70% of control heart rate. This bradycardia probably due to cardiac toxicity of bupivacaine because all of the bradycardia children used bupivacaine. 4) Poor risk children for general anesthesia such as upper respiratory tract infection, abnormal liver function test or congenital heart disease were sixteen among 103 children, and they all proceeded operative procedure without event. 5) Postoperative pain control was excellent in caudal anesthesia than general anesthesia according to pain-discomfort scale with 1 point vs 6 points at recovery room. With the above results we consider that pediatric caudal anesthesia is a safe and useful procedure with lesser complication especially in poor risk children.