Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

The Comparative Clinical Effects of Valsartan and Ramipril in Patients With Heart Failure

BACKGROUND AND OBJECTIVES: Angiotensin II receptor blocker (ARB) has emerged as an alternative to angiotensin converting enzyme inhibitor (ACEI) for the treatment of heart failure. This study aimed at comparing the effectiveness and safety of valsartan with ramipril in patients with heart failure, and these patients were hospitalized at Chonnam National University Hospital, Wonkwang University Hospital, Gunsan Medical Center, Presbyterian Medical Center, Seonam University Hospital and Gwangju Christian Hospital. SUBJECTS AND METHODS: Between March 2005 and March 2007, 82 patients (60.5+/-12.4 years, 59 males) who complained of class II to IV dyspnea, according to the New York Heart Association (NYHA) classification, and who had low left ventricular ejection fraction (LVEF) less than 50% were randomly allocated to valsartan or ramipril. After 6 months, the clinical symptoms, vital signs, biochemical tests and echocardiography were compared between the two groups. RESULTS: The NYHA class was improved in both groups (the valsartan group: 2.31+/-0.51 vs. 1.46+/-0.58, p<0.001; the ramipril group: 2.21+/-0.55 vs. 1.61+/-0.50, p<0.001). The incidence of cough, as measured by the cough index, was significantly lower in the valsartan group than in the ramipril group (p=0.045). The LVEF was improved in both groups (the valsartan group: 36.4+/-8.5% vs. 46.9+/-12.9%, p<0.001; the ramipril group: 35.1+/-8.5% vs. 45.3+/-11.2%, p<0.001). The improvements of the left ventricular end-systolic dimension (p=0.754) and end-diastolic dimension (p=0.998) were not different between the two groups. N-terminal Pro-B-type natriuretic peptide level was improved in both groups (the valsartan group: 2619.6+/-4213.5 vs. 995.4+/-2186.0 pg/mL, p=0.012; the ramipril group: 3267.9+/-4320.0 vs. 828.1+/-1232.8 pg/mL, p=0.009), and there was no difference between the groups (p=0.877). CONCLUSION: Both valsartan and ramipril were effective treatments, with relatively low adverse events, in patients with heart failure.

Nitric Oxide-Induced Intracellular Ca2+ Modulation in Macrovascular Endothelial Cells

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) reduces the intracellular Ca2+ concentration ([Ca2+]i) in smooth muscle cells, whereas the effect of NO on [Ca2+]i in endothelial cells is still controversial. Therefore, the effect of NO on the [Ca2+]i, and its mechanism in mouse aortic endothelial cells (MAEC) and human umbilical vein endothelial cells (HUVEC) were examined. MATERIALS AND METHODS: In primary cultured MAEC and HUVEC, cells were loaded with fura 2-AM and [Ca2+]i and measured using a microfluorometer. RESULTS: The NO donor, sodium nitroprusside (SNP), reduced the [Ca2+]i in 72% of the cells tested (n=100). In the remaining cells, the effect of SNP was biphasic, or the [Ca2+]i was increased. In addition, the membrane-permeable cGMP, 8-bromo cGMP, decreased the [Ca2+]i. The effects of SNP and 8-bromo cGMP were inhibited by the soluble guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one (ODQ), and the cGMP-dependent protein kinase inhibitor, KT5823, respectively. In contrast, in the presence of 8-bromo cGMP or ODQ, SNP increased the [Ca2+]i. CONCLUSION: These results suggest that NO inhibits the [Ca2+]i through a cGMP-dependent mechanism and increases the [Ca2+]i through a cGMP-independent mechanism.

Multiplane Transesophageal Echocardiographic Assessment of Left Atrial Appendage

BACKGROUND AND OBJECTIVES: Transesophageal echocardiography (TEE) allows a detailed evaluation of the structure and function of the left atrial appendage (LAA) by two-dimensional imaging and Doppler interrogation of appendage flow. LAA dysfunction has been associated with spontaneous echo contrast (SEC), thrombus formation and thromboembolism. The purpose of this study was to define normal heart reference values of LAA maximal forward velocity (LAAV), and to correlate LAAV with cardiac rhythm, mitral valve disease severity, SEC grade and left atrial thrombi development. SUBJECTS AND METHODS: LAA volume measurement and pulse Doppler evaluation of LA appendage flow during TEE were undertaken in 95 subjects; 32 patients with normal heart and 63 patients with various cardiac diseases. RESULTS: Mean LAAV was 87.1+/-26.7 cm/s, mean LAA maximal backward velocity 66.0+/-15.0 cm/s and mean LAA volume 2.2+/-1.2 mL in those patients with normal heart (n=32). There was a negative correlation between LAAV and SEC grade, mitral stenosis severity, LA size and LAA volume. Among those patients with atrial fibrillation, LAAV was lower in the subgroup with LA thrombi than in the subgroup without thrombi (14.9+/-8.1 cm/s (n=16), vs. 29.7+/-21.2 cm/s (n=33), p<0.01). CONCLUSION: Reduced LAAV, SEC and mitral stenosis are all associated with LAA thrombus formation in patients with atrial fibrillation.

Intravascular Ultrasound Findings of Coronary Wall Morphology in a Child with Kawasaki Disease

Intravascular ultrasound (IVUS) imaging was performed to assess the coronary wall morphology in detail at 22 months after the onset of Kawasaki disease in a girl who had developed coronary aneurysms at 4 yr of age. The sites of persistent aneurysms demonstrated a dilated lumen with a marked symmetrical or asymmetrical thickening of the intima-media complex. This pathologic finding was also present in angiographically normal vessels near an aneurysm but with a mild thickening. Coronary artery calcification was observed at one site in the aneurysms. The sites of normal coronary artery far from an aneurysm showed normal intravascular ultrasound findings with no measurable intima-media complex. Our case indicates that the healing process may continue via cell proliferation, with extension to the proximity of the coronary aneurysms. IVUS is useful to evaluate the coronary wall morphology and may be valuable in the long-term follow-up of coronary lesions due to Kawasaki disease.

Safety of transradial coronary intervention with early discharge in selected patients

BACKGROUND AND OBJECT: Transradial percutaneous coronary intervention enables early ambulation and caused less complications at the puncture site. This study was performed to evaluate the safety of transradial coronary intervention with early discharge in selected patients. MATERIALS AND METHOD: Thirty patients were studied retrospectively. Twenty five patients had transradial percutaneous coronary intervention with next morning discharge and 5 patients had transradial percutaneous coronary intervention on an outpatient basis. Each patient was checked for cardiovascular complication and any other problems at the puncture site immediately after, 2 weeks after and 1 month after the procedure. RESULTS: This study group consisted of 30 patients with a mean age of 60+/-10 years. The indication for intervention were unstable angina (63.3%), stable angina (20.0%), and restenosis at 6-month follow-up after intervention. A total of 21 stents were implanted at 40 lesions. No major cardiovascular complication nor puncture site complication was reported at 1 month follow-up. CONCLUSION: Early discharge is supposed to be safe for those with optimal angiographic results and no clinical problems for at least 5 hours after intervention.

Efficacy of Amiodarone in Tachycardia Induced Cardiomyopathy due to Non-Valvular Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Drug therapy to treat atrial fibrillation has been achieved unsatisfactory results due to the frequent failure to maintain a sinus rhythm as well as the occurrence of adverse side effects. This study investigated the efficacy of amiodarone for the treatment of tachycardia-induced cardiomyopathy due to non-valvular atrial fibrillation. SUBJECTS AND METHODS: We treated twenty-seven patients with tachycardia-induced cardiomyopathy due to non-valvular atrial fibrillation with amiodarone in order to convert to and maintain the sinus rhythm. We followed up and compared the functional status, electrocardiography and parameters of echocardiography before and after treatment with amiodarone. RESULTS: Patients treated with amiodarone showed cardiac functional improvement based on New York Heart Association classification. Eighteen patients (66.7%) out of the total 27 converted to sinus rhythm. The pulse rate decreased from 109.0+/-34 bpm (beats per min) before the administration of amiodarone to 70.3+/-13.0 bpm after medication. The size of the left atrium decreased from 50.7+/-6.7 (mm) to 46.9+/-5.6 (mm). The ejection fraction (EF) improved from 36.2+/-14.9 (%) to 51.2+/-17.7 (%). CONCLUSION: Amiodarone is effective in the conversion to sinus rhythm as well as ventricular rate control in patients with atrial fibrillation induced cardiomyopathy. The cardiac functional status and the echocardiographic parameters of left ventricular function in patients with tachycardia-induced cardiomyopathy due to atrial fibrillation improved with amiodarone therapy.

Prosthetic valve endocarditis manifesting multiple huge aspergilloma / 대한내과학회지

Fungal prosthetic valve endocarditis is a rare, poo-prognostic disease. The risk factors for fungal valve endocardits are open heart surgery, hyperalimentation, antibiotic therapy, IV drug abuse, concomitant bacterial endocarditis and immunosuppression. We report a case of aspergillus endocarditis in the aortic valve, which extended to ascending aorta after Redo-aortic valve replacement surgery. A 22-year-old male patient underwent Redo-aortic valve replacement surgery with 23mm-sized Sorin valve(bi-leaflet tilting disc valve) due to prosthetic valve failure. He was readmitted because of development of cough, anorexia, fatigue and fever after operation. The results of repeated blood culture were negative, and the symptoms continued in spite of 2 week treatment with broad spectrum antibiotics. Echocardiography and spiral computed tomographic angiography revealed multiple, huge masses in the aortic valve extending to ascending aorta. Emergent surgery was performed. Infected valve and surrounding areas were widely excised and aortic homograft was inserted. Resected aorta and prosthetic valve showed multiple mass-forming vegetations, measuring up to 4cmx3cmx3cm. Microscopically, they revealed fungal organisms, showing sharp-angle branching and septate hyphae. Aspergillus flavus was isolated in culture of resected tissue. The patient suddenly died of ventricular fibrillation 3 weeks after surgery in spite of treatement with intravenous amphotericin B.

The long-term follow-up results of the Electrical Cardioversion of Chronic Nonvalvular Atrial Fibrillation / 대한내과학회지

OBJECTIVES:We performed a prospective observation for the patients with chronic nonvalvular atrial fibrillation who underwent electrical cardioversion after failed pharmacological cardioversion with amiodarone. The aim of this study was to look at the immediate sinus conversion rate, the maintenance rate of sinus rhythm at long-term follow-up, and the clinical and echocardiographic parameters that influence on the rate of immediate sinus conversion and maintenance of sinus rhythm. At simultaneously, we intended to evaluate the efficacy of electrical cardioversion for the patients with chronic nonvalvular atrial fibrillation. METHODS: After anticoagulation therapy with coumadine for four weeks before cardioversion, we tried pharmacological cardioversion with amiodarone first. Failed cases included in this study. The direct current cardioversion was performed under transesophageal echocardiography monitoring to exclude the left atrial thrombus and to measure various echocardiographic parameters. After successful sinus cardioversion, we prescribed amiodarone with maintenance doses and coumadine at least 4 weeks. Transthoracic echocardiography was performed before cardioversion and one day, one month, 3 months, 6 months, and 9 months after sinus conversion. The minimum duration of atrial fibrillation was one month before the trial of pharmacological cardioversion. RESULTS: 1) The total number of patients was forty three (male: 28, female: 15, average age: 60+/-9). The initial success rate of sinus conversion was 88 %. 2) The maintenance rate of sinus rhythm with maintenance dose of amiodarone was 52 % after 9 months follow-up. 3) The direct current cardioversion was performed to 10 patients among 17 patients who recurred atrial fibrillation after sinus conversion. Among 10 patients, 5 patients of them were converted to sinus rhythm and maintained sinus rhythm after 9 months follow-up. 4) The initial success rate of sinus conversion was significantly higher in patients with lone atrial fibrillation compared with those patients with other associated heart disease (100 % vs. 83 %, p < 0.05), but the long-term maintenance rate of sinus rhythm was not influenced by the presence of associated disease. 5) The duration of atrial fibrillation before cardioversion was shorter in patients who were naintained sinus rhythm than that of those who were recurred atrial fibrillation. 6) The initial energy requirement at sinus conversion was lower in the patients who were maintained sinus rhythm than that of those who were recurred atrial fibrillation at 9 months follow-up. CONCLUSIONS: Direct current cardioversion was an effective treatment modality for patients with chronic nonvalvular atrial fibrillation after failure of pharmacological cardioversion with amiodarone.

The Effect of Hemodialysis on the Echocardiographic Indexes of Left Ventricular Diastolic Function in Chronic Renal Failure

BACKGROUND AND OBJECTIVES: The assessment of left ventricular (LV) diastolic function is important in chronic renal failure because abnormal LV diastolic function has been frequently described in patients on maintenance hemodialysis both during the dialysis and in the dialysis-free interval despite the normal LV systolic function. But the echocardiographic indexes of LV diastolic function is known to be affected by several factors such as loading condition, LV compliance and heart rate. The purpose of this study is to investigate the effect of hemodialysis on the echocardiographic indexes of left ventricular diastolic function in chronic renal failure. Materials AND METHODS: We examined transmitral flow velocity, pulmonary venous flow velocity, and mitral annulus velocity in 20 patients (15 men and 5 women, average 50+/-14, range 19-69 years) of chronic renal failure with normal LV systolic function by echocardiography before and after hemodialysis. RESULTS: 1)According to the body weight change (from 59.5+/-8.3 to 57.2+/-8.1 kg, p=0.0001), after hemodialysis, inferior vena cava dimension (from 18+/-4 to 13+/-5 cm, p=0.0001), left ventricular end-diastolic dimension (from 57+/-6 to 53+/-7 cm, p=0.0001), and left ventricular outflow tract (LVOT)-time velocity integral (TVI, from 26+/-5 to 23+/-5 cm, p=0.004), which reflect intravascular blood volume, decreased significantly. 2)The peak velocity of early transmitral flow (E, from 0.79+/-0.14 to 0.64+/-0.11 m/s, p=0.0001), the peak velocity of late transmitral flow (A, from 0.84+/-0.21 to 0.78+/-0.21 m/s, p=0.011), and E/A ratio (from 0.99+/-0.25 to 0.87+/-0.27, p=0.007) decreased significantly, and deceleration time (DT, from 241+/-48 to 267+/-59 ms, p=0.055) showed tendency of prolongation after hemodialysis. 3)Peak systolic velocity of pulmonary venous flow decreased significantly after hemodialysis (from 0.65+/-0.11 to 0.59+/-0.12 m/s, p=0.042). 4)The difference between duration of reversal flow of pulmonary vein and duration of transmitral flow during atrial contraction (ADD) did not change significantly after hemodialysis (from 5+/-31 to 1+/-29 ms, p=0.502), and did not correlate with the change of peak velocity of early transmitral flow during hemodialysis (DMVE, r=0.390, p=0.089). 5)The peak early diastolic velocity (Ean, from 0.07+/-0.02 to 0.06+/-0.02 m/s, p=0.002) and Ean/the peak late diastolic velocity (Aan) ratio (from 0.78+/-0.27 to 0.62+/-0.19, p=0.003) of medial annulus of mitral valve decreased significantly after hemodialysis. CONCLUSION: Hemodialysis, which reduces LV preload by fluid removal, changes the echocardiographic indexes of left ventricular diastolic function in chronic renal failure. Preload condition need to be accounted for when we evaluate the LV diastolic function with echocardiography.

A Case of Atrial Septal Aneurysm Associated with Multiple Renal Infarction

Atrial septal aneurysm (ASA) was reported as a cause of unknown origin of central or peripheral thromboembolism with patent foramen ovale, aortic debris and spontaneous echo contrast. Especially the paradoxical right to left shunt via micro-fenestration on this sac may be the important cause of this embolism. We report a case of 39 year-old female patient who had atrial septal aneurysm with multiple renal infarction. Symptom was improved with aneurysmectomy and patch closure, then long term anticoagulation has been continued.

A Case of Scimiter Syndrome (Adult Form) / 결핵

The scimitar syndrome, a rare complex anomaly, is defined as an anomalous right pulmonary venous drainage, partial or complete, to the inferior versa cava. The shape of the Turkish curved sword (scimitar) huts provided the name of this syndrome. Additional characteristics of this syndrome such as hypoplasia of the right lung and of the right pulmonary arterial tree, anomalous arterial supply of the right lung from the aorta, dextrocardia and bronchial anomalies are common. Recently we experienced a case of scimitar syndrome (adult form) in a 19-year-old woman patient, so we report the case with a brief review of the literature.

A Case of Osteogenesis Imperfecta associated with Aortic Regurgitation / 대한내과학회지

Osteogenesis imperfecta is one of the groups of hereditary disorders of connective tissue which includes the Ehlers-Danlos syndrome, the Marfan syndrome, pseudoxanthoma elasticum, and Hurler syndrome. While cardiovascular involvement is associated with each of these disorders, it is least common in osteogenesis imperfecta and is overshadowed by the bony, ocular, otologic, cutaneous, and dental manifestations that are characteristic of the disorder. In evaluating patients with osteogenesis imperfecta, careful attention should be paid to cardiovascular findings and if valvular lesions are noted, patients should be instructed regarding the need for antibiotic prophylaxis for dental and surgical procedures. We report a case of osteogenesis imperfecta associated with aortic regurgitation.

A Case of Takayasu's Arteritis Presented by Stenosis of Main Pulmonary Artery and Obstruction of the Right Coronary Artery / 대한내과학회지

Takayasu's arteritis is generally recognized as a chronic, idiopathic, inflammatory disease, which affects the aorta and the proximal portions of its major branches. We experienced a patient with Takayasu's arteritis who was presented with main pulmonary artery stenosis and right coronary ostial occlusion without involvement of aorta nor its major branches. She was managed with pulmonary arterioplasty and coronary artery bypass graft. This case emphasize that the disease cannot affect the aorta.

Percutaneous Mitral Balloon Valveloplasty after Successful Resolution of Left Atrial Appendage Thrombi by Oral Anticoagulation

OBJECTIVE: Systemic embolism related with left atrial thrombi is a well known complication of percutaneous ballon valveloplasty of the mitral valve stenosis. The presence of left atrial thtombi is believed to be a contraindication to balloon valvuloplasty. The purpose of this study was to determine whether balloon valvuloplasty is possible in mitral stenosis patients with left atrial thrombi after oral anticoagulation therapy. METHODS: We studied 13 consecutive patients(12 : female, 1 : male, mean age : 44+/-11) who had mitral stenosis and left atrial appendage thrombi by serial transesophageal echocardiography before balloon valvuloplasty of the stenotic mitral valve from May 1995 to January 1997. We started oral anticoagulation in those 13 patients with mitral stenosis and left atrial appendage thrombi to keep the INR 2-3. Regular follow up was performed by transesophageal echocardiagraphy to determine whether the left atrial appendage thrombi are resolved. Patients underwent percutaneous balloon valvuloplasty after complete resolution of left atrial appendage thrombi. RESULTS: 9 patients(69.2%) underwent balloon valvuloplasty after complete resolution of left atrial appendage thrombi with oral anticoagulation for average 6 months. Two (15.4%) patients had normal sinus rhythm. Three patients had coronary A-V fistular due to neovascularization to left atrial appendage thrombi. In four patients, oral antiocoagulation failed to resolve the left atrial appendage thrombi and they underwent balloon valvuloplasty under TEE guide with special caution to avoid systemic embolization. There were no complications such as systemic embolization in those 4 patients. CONCLUSION: Left atrial appendage thrombi in mitral stenosis could be resolved in high proportion(69.2%) by oral anticoagulation therapy. Percutaneous mitral balloon valvuloplasty could be a safe and effective treatment modality despite of the presence of left atrial appendage thrombi after adequate oral anticoagulation therapy.