Protriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

In this study, we explore the inhibitory effects of protriptyline, a tricyclic antidepressant drug, on voltage-dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Protriptyline inhibited the vascular Kv current in a concentration-dependent manner, with an IC50 value of 5.05 ± 0.97 µM and a Hill coefficient of 0.73 ± 0.04. Protriptyline did not affect the steady-state activation kinetics. However, the drug shifted the steady-state inactivation curve to the left, suggesting that protriptyline inhibited the Kv channels by changing their voltage sensitivity. Application of 20 repetitive train pulses (1 or 2 Hz) progressively increased the protriptyline-induced inhibition of the Kv current, suggesting that protriptyline inhibited Kv channels in a use (state)-dependent manner. The extent of Kv current inhibition by protriptyline was similar during the first, second, and third step pulses. These results suggest that protriptyline-induced inhibition of the Kv current mainly occurs principally in the closed state. The increase in the inactivation recovery time constant in the presence of protriptyline also supported use (state)-dependent inhibition of Kv channels by the drug. In the presence of the Kv1.5 inhibitor, protriptyline did not induce further inhibition of the Kv channels. However, pretreatment with a Kv2.1 or Kv7 inhibitor induced further inhibition of Kv current to a similar extent to that observed with protriptyline alone. Thus, we conclude that protriptyline inhibits the vascular Kv channels in a concentration- and use-dependent manner by changing their gating properties. Furthermore, protriptyline-induced inhibition of Kv channels mainly involves the Kv1.5.

Comparison of three rapid influenza diagnostic tests with digital readout systems and one conventional rapid influenza diagnostic test.

BACKGROUND: Rapid influenza diagnostic tests (RIDTs) show variable sensitivities in clinical settings. We aimed to compare three digital RIDTs and one conventional RIDT. METHODS: We assessed 218 nasopharyngeal swabs from patients between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test results were compared with those from the Anyplex Flu A/B Typing Real-time Detection real-time PCR. The four RIDTs were tested with diluted solutions from the National Institute for Biological Standards and Control (NIBSC) to compare lower detection limit. Cross-reactivity of four RIDTs within other respiratory viruses was identified. RESULTS: For influenza A, BUDDI, Sofia, Veritor, and Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%, 96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and 100% specificity, respectively. Each RIDT could detect diluted NIBSC solution, according to the level of dilution and specific influenza subtypes. Cross-reactivity of four RIDTs with other respiratory viruses was not noted. CONCLUSIONS: Sofia showed the highest sensitivity for influenza A and B detection. BUDDI and Veritor showed higher detection sensitivity than a conventional RIDT for influenza A detection, but similar results for influenza B detection. Further study is needed to compare the test performance of RIDTs according to specific, prevalent influenza subtypes.

Nonaneurysmal infectious aortitis.

Infectious aortitis is a rare disease in the antibiotic era. Only a small number of cases of nonaneurysmal infectious aortitis are discussed in literature, and its true incidence and natural history are not well defined. We present here a case of typical nonaneurysmal infectious aortitis with literature review of 19 cases of aortic infection in which the aorta is initially normal in caliber.

Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers.

Cigarette smoke (CS) poses a significant risk factor for respiratory, vascular, and organ diseases owing to its high content of harmful chemicals and reactive oxygen species (ROS). These substances are known to induce oxidative stress, inflammation, apoptosis, and senescence due to their exposure to environmental pollutants and the presence of oxidative enzymes. The lung is particularly susceptible to oxidative stress. Persistent oxidative stress caused by chronic exposure to CS can lead to respiratory diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), and lung cancer. Avoiding exposure to environmental pollutants, like cigarette smoke and air pollution, can help mitigate oxidative stress. A comprehensive understanding of oxidative stress and its impact on the lungs requires future research. This includes identifying strategies for preventing and treating lung diseases as well as investigating the underlying mechanisms behind oxidative stress. Thus, this review aims to investigate the cellular processes induced by CS, specifically inflammation, apoptosis, senescence, and their associated biomarkers. Furthermore, this review will delve into the alveolar response provoked by CS, emphasizing the roles of potential therapeutic target markers and strategies in inflammation and oxidative stress.

Tuberculosis-Infected Giant Bulla Treated by Percutaneous Drainage Followed by Obliteration of the Pulmonary Cavity Using Talc: Case Report.

Tuberculosis (TB)-infected giant bullae are rare. A 55-year-old man was referred when an infected bulla did not respond to empirical treatment. Computed tomography showed a giant bulla in the right upper lobe with an air-fluid level and surrounding infiltrate. Sputum culture, acid-fast bacilli (AFB) stain, and polymerase chain reaction (PCR) for TB were negative. Percutaneous drainage of the bullous fluid was performed. AFB stain and PCR were positive in the drained fluid. The patient was given anti-TB drugs and later underwent obliteration of the pulmonary cavity using talc. To summarize, we report a patient with a TB-infected giant bulla that was treated successfully with anti-TB drugs and obliteration of the pulmonary cavity using talc.

Myocardial protective effect of tezosentan, an endothelin receptor antagonist, for ischemia-reperfusion injury in experimental heart failure models.

The myocardial protective effects of endothelin antagonist in ischemic cardiomyopathy (ICMP), doxorubicin-induced cardiomyopathy (DOX) and pressure-overload hypertrophy by transverse aortic constriction (TAC) models have been predicted to be different. The objective of this experiment, therefore, is to evaluate the myocardial protective effect of tezosentan, an endothelin receptor antagonist, in various experimental heart failure models. Sprague-Dawley rats (6-8 weeks old, 200-300 g) were randomized to three experimental groups (n=30 each): ICMP; DOX; and TAC group. Each of these groups was randomly assigned further to the following subgroups (n=10 each): sham-operated ischemia-reperfusion subgroup (SHAM); tezosentan treated ischemia-reperfusion subgroup (Tezo); and tezosentan non-treated ischemia-reperfusion subgroup (N-Tezo). Total circulatory arrest was induced for 1 hr, followed by 2 hr of reperfusion. The left ventricular developed pressure, peak positive and negative first derivatives, and coronary blood flow were significantly different (P<0.05) among the SHAM, Tezo, and N-Tezo subgroups of the ICMP group at 30 min of reperfusion, but there were no statistically significant differences among the subgroups of the DOX and TAC groups. In conclusion, tezosentan, an endothelin receptor antagonist, showed myocardial protection effects only on the ischemic cardiomyopathy rat model, but not in the non-ischemic heart failure rat models.

Bleomycin Inhibits Proliferation via Schlafen-Mediated Cell Cycle Arrest in Mouse Alveolar Epithelial Cells.

BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. METHODS: Mouse AE II cell line MLE-12 were exposed to 1-10 µg/mL BLM and 0.01-100 µM baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. RESULTS: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor α, and transforming growth factor ß1. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. CONCLUSION: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

Unexpected complication during extracorporeal membrane oxygenation support: Ventilator associated systemic air embolism.

Systemic air embolism through a bronchovenous fistula (BVF) has been described in patients undergoing positive-pressure ventilation. However, no report has mentioned the potential risks of systemic air embolism through a BVF in patients undergoing extracorporeal membrane oxygenation (ECMO). Positive-pressure ventilation and ECMO support in patients with lung injury can increase the risk of systemic air embolism through a BVF. Increased alveolar pressure, decreased pulmonary venous pressure, and anticoagulation are thought to be the factors that contribute to this complication. Here, we present a case of systemic air embolism in a patient with ECMO and mechanical ventilator support.

L-carnosine induces apoptosis/cell cycle arrest via suppression of NF-κB/STAT1 pathway in HCT116 colorectal cancer cells.

L-carnosine, a dipeptide of the amino acids ß-alanine and histidine, is found in various tissues, such as the central nervous system and skeletal muscles. Recently, L-carnosine has been reported to possess anti-tumor activity; however, the molecular mechanism underlying its activity in colorectal cancer is still unknown. Therefore, we investigated the effect of L-carnosine using a human colorectal cancer cell line, HCT116. Treatment with L-carnosine (0, 100, or 200 mM) for 24 h gradually reduced cellular proliferation according to immunochemistry and 7-aminoactinomycin D (7-AAD) analyses and induced G0/G1 phase arrest. In the RT-PCR analysis, L-carnosine decreased the mRNA levels of cell cycle-related genes in HCT116 cells. In the Western blot analysis, levels of the cyclin D1, BAX/Bcl-2, cleaved caspase-3, p21, and p53 proteins were significantly increased in cells treated with L-carnosine. We next determined whether STAT1/NF-κB pathway is involved in regulation of cell cycle arrest- and cell death-associated gene in HCT116. The L-carnosine treatment significantly inhibited the phosphorylation of STAT1 on Tyr701 and NF-κB p65 on Ser276 and Ser536, and then, we exogenously blocked the NF-κB phosphorylation using Bay 11-7082. Based on our findings, L-carnosine induces cell cycle arrest and apoptosis in human colorectal cancer cells by suppressing of NF-κB/STAT1 signaling.

Upper extremity ischemia from developmental failure of brachial artery-a case report.

Advances in medicine and technology have increased brachial artery utilization for diagnostic and interventional radiology. Hence, detection and assessment of variations in upper extremity vasculature are important regardless of the low surgical intervention rate in the upper extremity. Anomalies of the upper extremity artery are infrequently reported, and anomalies of the brachial artery are even less common. Presented here is a case of developmental failure of the brachial artery. A segment about 2.1 cm from its origin was treated with bypass surgery. This is presented as an uncommon variation of the brachial artery.

A treatment case of delayed aortic injury: the patient with posterior rib fracture.

A 66-year-old male patient arrived at the emergency room with a crush injury to his chest. Multiple rib fractures, hemothorax on both sides, left scapular fracture, liver laceration, and retroperitoneal hematoma were found upon the radiologic examination. After closed thoracostomy, the patient had been initially admitted to the intensive care unit, but he was transferred to the general ward on the next day. On the 4th post-trauma day, the patient complained of severe pain and there was bloody drainage through the chest tube. This case is an exploration with the consideration of the possibility of major bleeding and the subsequent repair of the descending thoracic aorta. This case is regarded as a case in which the aorta wall was damaged as the sharp margin of the fractured ribs caused continuous irritation.

A treatment case of endoscopic removal of left ventricular thrombus, during coronary artery bypass graft.

Left ventricular thrombus is a common complication related to acute myocardial infarction. Removing this with an incision of the free wall of the left ventricle may cause fatal cardiac dysfunction or arrhythmias. Furthermore, performing incision and suture on the fragile myocardium of an acute myocardial infarction patient may cause serious bleeding complications. If there is a patient with left ventricular thrombus who needs thoracotomy for another reason, the case is attempted with the thought that if effective intraventricular visualization and manipulation can be done, fatalities caused by incision and suture may be reduced. For patients undergoing cardiopulmonary bypass, if intracardiac manipulation is required, an endoscope can be used, and given the potential complications after the incision and suturing of the infarcted tissue, the benefits are deemed sufficient.

Analysis of the effect of renal replacement therapy: in the prolonged extracorporeal membrane oxygenation patients.

BACKGROUND: This paper aimed to verify the effects of renal replacement therapy on changing the levels of serum creatinine for different veno-arterial and veno-venous configurations in prolonged extracorporeal membrane oxygenation (ECMO) patients. METHODS: The subjects were chosen 71 patients who had undergone more than 1,440 minutes (24 hours) of the therapy from among 117 patients who had undergone ECMO insertion between January 2008 and December 2012. The patients were separated into the veno-arterial configuration group I (51 patients) and the veno-venous configuration group II (20 patients). The difference in the level of serum creatinine (ΔCr) between before or just after ECMO insertion (CrI) and the level when the pump time was between 2,880 and 4,320 minutes (CrF) was checked (ΔCr=CrF-CrI), and the average ΔCr for each group was compared using a Student t-test at the confidence interval (CI) of 95%. RESULTS: The change in the level of serum creatinine was an increase of 0.341 mg/dL (σ=0.9202) for group I and a decrease of 0.120 mg/dL (σ=1.5292) for group II. The change was significantly high for group I (p=0.011, CI=95%). Meanwhile, within group I, when renal replacement therapy was not done, there was a significant increase in the level of serum creatinine (p=0.009, CI=95%). CONCLUSION: For ECMO insertion patients whose pump time was more than 1,440 minutes, there was a significant change in the level of serum creatinine when renal replacement therapy was not done, for the veno-arterial configuration of group I.

Nicotine inhibits the proliferation by upregulation of nitric oxide and increased HDAC1 in mouse neural stem cells.

Cigarette smoking (CS) is considered one of the major risk factors to cause neurodegenerative disorders. Nicotine is the main chemical in CS which is responsible for dysfunction of the brain as a neuroteratogen. Also, nicotine dependency is a real mental illness and disease. Recently, chronic nicotine exposure has been shown to cause oxidative/nitrosative stress leading to a deleterious condition to cellular death in different brain regions. However, little is known about the effects of nicotine on mouse neural stem cells (mNSCs). The aim of this study is to investigate the effects of nicotine on mNSCs and elucidate underlying mechanisms involved in expression of a diversity of genes regulated by nicotine. When mNSCs were isolated from the whole brain of embryonic day 16 mice treated with nicotine at vehicle, 100, 400, and 800 µM for 5 d, nicotine significantly decreased the number and size of neurospheres. In immunocytochemistry, nicotine-exposed mNSCs expressing nestin showed the shortened filaments and condensed nuclei. In RT-PCR, messenger RNA (mRNA) levels of proliferating cell nuclear antigen (PCNA) and sirtuin1 (SIRT1) were significantly decreased, while the production of nitric oxide and mRNA levels of cyclooxygenase2 (COX-2), tumor necrosis factor-alpha TNF-α, and histone deacetylase 1 (HDAC1) were increased in a dose-dependent manner. In addition, sodium butyrate and valproic acid, HDAC inhibitors, partially rescue proliferation of mNSCs via inhibition of HDAC1 expression and NO production. Taken together, these data demonstrate that prolonged exposure of nicotine decreased proliferation of mNSCs by increased NO and inflammatory cytokine through increased HDAC1. Furthermore, this study could help in the development of a therapy for nicotine-induced neurodegenerative disorder and drug abuse.

Cardiac tamponade complicated by acupuncture: hemopericardium due to shredded coronary artery injury.

We report a case of 62-year-old man with cardiac tamponade due to coronary artery injury after acupuncture into the substernum. After resuscitation of cardiac arrest, we performed emergent pericardiocentesis. Nevertheless, the cardiac arrest recurred, and the emergent operation on cardiopulmonary bypass was performed. We identified hemopericardium due to shredded acute marginal branch of right coronary artery, and it was ligated leading to termination of bleeding. The patient was discharged without any other complications.

The effect of distal aortic pressure on spinal cord perfusion in rats.

BACKGROUND: Aortic cross clamping is associated with spinal cord ischemia. This study used a rat spinal cord ischemia model to investigate the effect of distal aortic pressure on spinal cord perfusion. MATERIALS AND METHODS: Male Sprague-Dawley rats (n=12) were divided into three groups. In group A (n=4), the aorta was not occluded. In groups B (n=4) and C (n=4), the aorta was occluded. In group B the distal aortic pressures dropped to around 20 mmHg. In group C, the distal aortic pressure was decreased to near zero. The carotid artery and tail artery were cannulated to monitor the proximal aortic pressure and the distal aortic pressure. Fluorescent microspheres were used to measure the regional blood flow in the spinal cord. RESULTS: After aortic occlusion, blood flow to the cervical spinal cord showed no significant difference among the three groups. In groups B and C, the thoracic and lumbar spinal cord and renal blood flow decreased. No microspheres were detected in the thoracic and lumbar spinal cord of group C. CONCLUSION: The spinal cord blood flow is dependent on the distal aortic pressure after thoracic aortic occlusion.

A surgically treated case of chronic necrotizing aspergillosis with pleural invasion.

Aspergillus is a ubiquitous fungus and can cause many levels of disease severity. Chronic necrotizing aspergillosis is a rare disease and few cases have been reported in Korea. We experienced a case of pleural aspergillosis that was treated successfully with medical and surgical interventions. The 52-year-old man who was diagnosed with chronic necrotizing pulmonary aspergillosis underwent surgical treatment including a lobectomy, decortication, and myoplasty. The patient was also medically treated with amphotericin B followed by voriconazole. Pleural irrigation with amphotericin B was also performed. A multi-dimensional approach should be considered for treating chronic necrotizing pulmonary aspergillosis.

Fluid-filled Giant Bulla Treated with Percutaneous Drainage and Talc Sclerotherapy: A Modified Brompton Technique.

A 75-year-old man who was diagnosed as having a fluid-filled giant bulla was treated with a modified Brompton technique due to his poor performance status. Percutaneous drainage, suction, and talc sclerotherapy through a Foley catheter can be good treatment options for patients with conditions that are too poor to allow surgical intervention, especially if there is adhesion between a giant bulla and parietal pleura. Talc can also be used safely when mixed with normal saline as a sclerosant.

Thoracic outlet syndrome after the Nuss procedure for the correction of extreme pectus excavatum.

Since the Nuss procedure was introduced in 1998, many complications have been reported, but not thoracic outlet syndrome. Here we report a 13-year-old boy with pectus excavatum who had thoracic outlet syndrome develop after a modified Nuss procedure. The major modification from the original technique was the use of an additional bar to resolve his long, asymmetric deformity. The patient showed clinical features of brachial plexus compression. The abrupt structural and spatial changes induced by the marked elevation of the upper depressed chest might have given rise to this condition. Thoracic outlet syndrome is a possible complication of the Nuss procedure.

A comparative study of pericostal and submuscular bar fixation technique in the Nuss procedure.

We evaluated the safety and stability of the less-invasive submuscular bar fixation method in the Nuss procedure. One hundred and thirteen patients undergoing the Nuss procedure were divided into three groups according to the bar fixation technique employed. Group 1 consisted of 25 patients who had undergone bilateral pericostal bar fixation, group 2 consisted of 39 patients with unilateral pericostal one, and group 3 included 49 patients with bilateral submuscular one. The patients' age ranged from 2 to 25 yr, with an average of 7.2+/-5.67 yr. Bar dislocation occurred in 1 patient (4%) in Group 1, 2 patients (5.1%) in Group 2, and 1 patient (2.0%) in Group 3 (p=0.46). Hemothorax was noted in 2 patients (8%) in Group 1, 2 (5.1%) in Group 2, and none (0%) in Group 3 (Group 1 vs. Group 3, p=0.028). The mean operation time was shorter in Group 3 than Group 1 (50.1+/-21.00 in Group 3 vs. 67.2+/-33.07 min in Group 1, p=0.041). The submuscular bar fixation results in a decrease in technique-related complications and operation time and is associated with favorable results with regard to the prevention of bar dislodgement.