Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB-MITF-tyrosinase signalling pathway in melanocytes.

Ginsenosides are major active components of ginseng, and have diverse pharmacological properties in traditional medicine. Recent reports have shown that ginsenosides modify skin physiology and mitigate skin disorders such as photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of protopanaxatriol, a major category of ginsenosides, as a depigmenting agent. Protopanaxatriol significantly reduced intracellular and extracellular melanin content in a concentration-dependent manner in B16 melanoma cells treated with α-melanocyte-stimulating hormone. In normal human epidermal melanocytes, protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In addition, protopanaxatriol dramatically suppressed the expression of genes encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and -2, and microphthalmia-associated transcription factor through dephosphorylation of cAMP response element-binding protein. These results suggest that protopanaxatriol could be an effective candidate anti-melanogenic agent.

Clinical significance of QT-prolonging drug use in patients with MDR-TB or NTM disease.

SETTING: Many drugs with potential QT prolongation effects (QT drugs) have already been used for decades in patients with multidrug-resistant TB (MDR-TB) or non-tuberculous mycobacterial (NTM) disease, but without a common consensus. OBJECTIVE: To investigate the effects of QT drugs on cardiac events in patients with MDR-TB or NTM disease. METHODS: We retrospectively reviewed 373 patients (mean age: 56.4 years) with MDR-TB or NTM disease treated for >1 month with clofazimine (CFZ), moxifloxacin (MFX), bedaquiline (BDQ), delamanid (DLM) or macrolides (clarithromycin or azithromycin). Adverse cardiac events, death and QTcF changes were evaluated. RESULTS: Forty-four per cent had MDR-TB; 165 (44%), 315 (85%), 10 (3%), 229 (61%) and 1 patient received CFZ, MFX, BDQ, macrolides and DLM, respectively. Except for three patients (0.8%) lost to follow-up with unknown cause of death, 3 (0.8%, 95%CI 0.2-2.4) adverse cardiac events were documented: atrial fibrillation, cardiac tamponade due to TB pericarditis and cardiac arrest, which was determined to not have been caused by QT drugs. Clinically significant QTcF changes (QTcF > 500 msec or an increase > 60 msec) were observed in 10/60 patients (17%, 95%CI 8.0-30.7) without clinical events. CONCLUSION: The use of QT drugs, alone or in combination, in the treatment of MDR-TB or NTM disease is relatively safe.

Phosphatidylinositol 4,5-bisphosphate is acting as a signal molecule in alpha(1)-adrenergic pathway via the modulation of acetylcholine-activated K(+) channels in mouse atrial myocytes.

We have investigated the effect of alpha(1)-adrenergic agonist phenylephrine (PE) on acetylcholine-activated K(+) currents (I(KACh)). I(KACh) was recorded in mouse atrial myocytes using the patch clamp technique. I(KACh) was activated by 10 microm ACh and the current decreased by 44.27 +/- 2.38% (n = 12) during 4 min due to ACh-induced desensitization. When PE was applied with ACh, the extent of desensitization was markedly increased to 69.34 +/- 2.22% (n = 9), indicating the presence of PE-induced desensitization. I(KACh) was fully recovered from desensitization after a 6-min washout. PE-induced desensitization of I(KACh) was not affected by protein kinase C inhibitor, calphostin C, but abolished by phospholipase C (PLC) inhibitor, neomycin. When phophatidylinositol 4,5-bisphosphate (PIP(2)) replenishment was blocked by wortmannin (an inhibitor of phophatidylinositol 3-kinase and phophatidylinositol 4-kinase), desensitization of I(KACh) in the presence of PE was further increased (97.25 +/- 7.63%, n = 6). Furthermore, the recovery from PE-induced desensitization was inhibited, and the amplitude of I(KACh) at the second exposure after washout was reduced to 19.65 +/- 2.61% (n = 6) of the preceding level. These data suggest that the K(ACh) channel is modulated by PE through PLC stimulation and depletion of PIP(2).

Restoration of atrial mechanical function after successful radio-frequency catheter ablation of atrial flutter.

BACKGROUND: Atrial mechanical dysfunction and its recovery time course after successful radiofrequency ablation of chronic atrial flutter (AFL) has been largely unknown. We serially evaluated left atrial function by echocardiography after successful ablation of chronic atrial flutter. METHODS: In 13 patients with chronic AFL, mitral E wave A wave, and the ratio of A/E velocity were measured at 1 day, 1 month, 3 months and 6-12 months after successful radiofrequency (RF) ablation. Doppler tissue imaging (DTI) technique was also used to avoid load-dependent variation in the flow velocity pattern. RESULTS: Left atrial mechanical function, assessed by A wave velocity and the annular motion, was depressed at 1 day, but improved significantly at 1 month and maintained through 6-12 months after the ablation. Left atrial size did not change significantly. CONCLUSION: Left atrial mechanical function was depressed immediately after successful RF ablation of chronic AFL, but it improved significantly after 1 month and was maintained over one year.

Successful management of mechanical complications following acute myocardial infarction--a case report.

Rupture of the heart as a complication of myocardial infarction is one of the most common causes of in-hospital mortality. Rupture of the free wall of the ventricle or interventricular septum has a poor prognosis when treated conservatively. So, rupture of the heart after infarction requires prompt diagnosis and early surgical repair despite the high overall incidence of early operative mortality before hemodynamic deterioration and multiorgan failures develop. Rupture of the left ventricle results in pseudoaneurysm if the overlying pericardium adhers to the surface of the heart. Pseudoaneurysms which rarely develop after infarction, tend to rupture. Their presence alone is an indicator for operation because of the very poor prognosis following rupture. We experienced successful management of 2 rare complications after acute myocardial infarction: ventricular septal defect and pseudoaneurysm. The first patient was a 49-year-old man who had an apical septal defect. His electrocardiogram showed Q wave in leads V2-V6, II, III, and aVF but a coronary angiogram showed normal findings. He was successfully treated by patch closure of the septal defect. The second patient was a 65-year-old female who had false aneurysm of the left ventricle. She had neither chest pain nor abnormality on the electrocardiogram. A coronary angiogram showed complete occlusion of the distal circumflex artery. Under cardiopulmonary bypass, the neck of the aneurysmal sac was successfully closed with a prolene suture.

Temperature-guided radiofrequency catheter ablation of accessory pathway.

OBJECTIVES: This study was performed to evaluate the usefulness of temperature-guided radiofrequency catheter ablation for the elimination of accessory pathway conduction in patients with Wolff-Parkinson-White syndrome. METHODS: Temperature-guided radiofrequency catheter ablation was attempted in 138 patients with 144 accessory pathways (88 pathways along the left free wall, 5 in the anteroseptal region, 2 in the midseptal region, 19 in the posteroseptal region and 30 along the right free wall). The energy source was a HAT 200S which regulated the power automatically to the set temperature of 70 degrees C. Radiofrequency current was delivered through a thermocatheter to the atrial or ventricular side of mitral or tricuspid annulus. RESULTS: Accessory pathway conduction was eliminated in 130 of 144 pathways (90.3%). The mean power outputs of the successful ablations at the atrial side of the annulus were higher than those at the ventricular side (34.0 +/- 8.9W versus 20.0 +/- 7.6W, p < 0.01), but the maximum temperatures were lower at the atrial side of the annulus than those at the ventricular side (66.4 +/- 14.0 degrees C versus 77.2 +/- 6.4 degrees C, p < 0.01). There were 3 non-fatal complications (2.1%), 2 patients with hemopericardium and 1 with femoral artery thrombus, during or after ablation procedures. Recurrences of AV re-entrant tachycardia or delta wave on the electrocardiogram occurred in 4 patients (2.8%) who had successful second procedures. There were no late complications during a mean follow-up period of 41 +/- 25 months (range, 3 to 55). CONCLUSION: We conclude that 1) temperature-guided radiofrequency catheter ablation can be performed reliably and safely in eliminating accessory pathway conduction in patients with WPW syndrome, and 2) temperature monitoring and adjustment of the power to the set temperature during ablation would be useful for the avoidance of impedance rises and coagulum formation.

Clinical characteristics of constrictive pericarditis diagnosed by echo-Doppler technique in Korea.

A retrospective analysis of clinical data of 71 patients with constrictive pericarditis (CP) diagnosed by echo-Doppler technique (mean age, 49+/-17) was done. In 27 patients (38%), the etiology was unknown, and the three most frequent identifiable causes were tuberculosis (23/71, 32%), cardiac surgery (8/71, 11%), and mediastinal irradiation (6/71, 9%). Pericardiectomy was performed in 35 patients (49%) with a surgical mortality of 6% (2/35), and 11 patients (15%, 11/ 71) showed complete resolution of constrictive physiology with medical treatment. Patients with transient CP were characterized by absence of pericardial calcification, shorter symptom duration, and higher incidence of fever, weight loss, and tuberculosis. The 5-yr survival rates of patients with transient CP and those undergoing pericardiectomy were 100% and 85+/-6%, respectively, which were significantly higher than that of patients without undergoing pericardiectomy (33+/-17%, p=0.0083). Mediastinal irradiation, higher functional class, low voltage in ECG, low serum albumin, and old age were the independent variables associated with a higher mortality. Tuberculosis is still the most important etiology of CP in Korea, and not infrequently, it may cause transient CP. Early diagnosis and decision-making using follow-up echocardiography are crucial to improve the prognosis of patients with CP.