Pentazocine Inhibits Norepinephrine Transporter Function by Reducing its Surface Expression in Bovine Adrenal Medullary Cells

(±)-Pentazocine (PTZ), a non-narcotic analgesic, is used for the clinical management of moderate to severe pain. To study the effect of PTZ on the descending noradrenergic inhibitory system, in the present study we examined the effect of [³H]norepinephrine (NE) uptake by cultured bovine adrenal medullary cells and human neuroblastoma SK-N-SH cells. (?)-PTZ and (+)-PTZ inhibited [³H]NE uptake by adrenal medullary cells in a concentration-dependent (3 – 100 μM) manner. Eadie-Hofstee analysis of [³H]NE uptake showed that both PTZs caused a significant decrease in the V_max with little change in the apparent K_m, suggesting non-competitive inhibition. Nor-Binaltorphimine and BD-1047, κ-opioid and σ-receptor antagonists, respectively, did not affect the inhibition of [³H]NE uptake induced by (?)-PTZ and (+)-PTZ, respectively. PTZs suppressed specific [³H]nisoxetine binding to intact SK-N-SH cells, but not directly to the plasma membranes isolated from the bovine adrenal medulla. Scatchard analysis of [³H]nisoxetine binding to SK-N-SH cells revealed that PTZs reduced the B_max without changing the apparent K_d. Western blot analysis showed a decrease in biotinylated cell-surface NE transporter (NET) expression after the treatment with (?)-PTZ. These findings suggest that PTZ inhibits the NET function by reducing the amount of NET in the cell surface membranes through an opioid and σ-receptor–independent pathway.     

FR167653 attenuates ischemia and reperfusion injury of the rat lung with suppressing p38 mitogen-activated protein kinase.

BACKGROUND: FR167653 is a potent suppressant of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1) production, and was shown to attenuate ischemia and reperfusion (I/R) organ injury in our previous experiment. Because p38 mitogen-activated protein (MAP) kinase has been reported to regulate the production of TNF-alpha and IL-1, we examined the effects of FR167653 in the rat lung I/R model and determined the expression and activation of p38 MAP kinase. METHODS: Experiment 1: After 1 hour of ischemia, p38 MAP kinase, phosphorylated p38 MAP kinase (active form), histologic changes of the lung, and serum levels of TNF-alpha and IL-1beta were examined. Experiment 2: After 2 hours of reperfusion, arterial oxygen content (PaO(2)) and saturation (SaO(2)), serum TNF-alpha and IL-1beta levels, and histologic changes in the lung were examined. Rats were divided into three groups in Experiment 1. In the control group, a saline solution was administered and, in the FR group, 0.1 mg/kg per hour of FR167653 was administered, intravenously throughout the experiment, beginning 30 minutes before ischemia. In the non-ischemic group, samples were taken soon after thoracotomy. The rats were divided into control and FR groups in Experiment 2. RESULTS: Experiment 1: One hour of ischemia induced almost no changes in the lung or serum cytokine levels. Meanwhile, FR167653 markedly attenuated the expression of phosphorylated p38 MAP kinase. Experiment 2: SaO(2) and PaO(2) were improved, serum cytokines were lower, and lung damage was less extensive in the FR group than in the control group. CONCLUSION: FR167653 attenuates I/R injury of the lung and this attenuation is associated with suppression of p38 MAP kinase activation.     

PR interval prolongation is significantly associated with aortic root abscess: An age‐ and gender‐matched study

BackgroundElectrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age‐ and gender‐matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis.MethodsPatients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12‐lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre‐ and post‐admission PR interval, was the primary outcome of interest. The patients in the ARA group were age‐ and gender‐matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed.ResultsEighteen patients with surgically confirmed ARA were enrolled. These patients were age‐ and gender‐matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (−5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003).ConclusionsThe findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement.     

Effect of landiolol hydrochloride, an ultra-short-acting beta 1-selective blocker, on supraventricular tachycardia, atrial fibrillation and flutter after pulmonary resection

What is known and objective: Supraventricular tachycardia is a common complication after pulmonary resection. The objective of this study was to investigate the efficacy of landiolol hydrochloride, an ultra‐short‐acting β1‐blocker, in patients with post‐operative supraventricular tachycardia after pulmonary resection. Methods: The response to continuous intravenous infusion of landiolol was evaluated in 25 patients who developed post‐operative atrial fibrillation or atrial flutter after major pulmonary resection. Four patients had preoperative rate‐controlled chronic atrial fibrillation. The heart rate and blood pressure were compared before and after infusion of landiolol. Side effects and recurrence of supraventricular tachycardia after termination of landiolol infusion were also monitored. Results and discussion: The heart rate was reduced from 135 ± 24 bpm before landiolol infusion to a plateau rate of 85 ± 19 bpm during infusion (P < 0·0001). Heart rate reduction occurred in all but two patients. Conversion to normal sinus rhythm from supraventricular tachycardia occurred in 14 patients (56%). Recurrence of supraventricular tachycardia after stopping landiolol infusion was observed in 17 patients (68%), but all patients without preoperative AF were cured of post‐operative AF. There were no detectable side effects, including no adverse influence on the circulatory and respiratory systems. What is new and conclusion: Continuous intravenous infusion of landiolol was found to be effective and safe for supraventricular tachycardia after pulmonary resection.     

Aortic Insufficiency and Hemocompatibility-related Adverse Events in Patients with Left Ventricular Assist Devices

AimHemocompatibility-related adverse events (HRAE) are a major cause of readmissions in patients with left ventricular assist devices (LVAD). The impact of aortic insufficiency (AI) on HRAE remains uncertain. We aimed to investigate the impact of AI on HRAE.Methods and ResultsPatients who underwent LVAD implantation between August 2014 and July 2017 and had echocardiograms 3 months post-LVAD implantation were enrolled. AI severity was assessed by measuring the systolic/diastolic ratio of flow and the rate of diastolic flow acceleration using Doppler echocardiography of the outflow cannula. Regurgitation fraction was derived from these parameters. Significant AI was defined as regurgitation fraction > 30%. Among 105 patients (median age, 56 years; 76% male), 36 patients (34%) had significant AI. Baseline characteristics were statistically not significantly different between those with and without significant AI except for higher rates of ischemic etiology and atrial fibrillation in the significant AI group (P < 0.05 for both). One-year survival free from HRAE was 44% in patients with AI compared to 67% in patients without significant AI (P = 0.018). The average hemocompatibility score, which defines the net burden of HRAE, was higher in the AI group (1.72 vs 0.64; P = 0.009), due mostly to higher tier I (mild HRAE; P = 0.034) and tier IIIB scores (severe HRAE; P = 0.011).ConclusionSignificant AI, as assessed by Doppler echocardiographic parameters, was associated with HRAE during LVAD support.     

High-grade fetal adenocarcinoma of the lung; report of a case

82-year-old man was admitted with an abnormal shadow on the chest roentgenogram. Computed tomography showed a 2.8 x 2.4 cm solid tumor in S3 of the left lung. Transbronchial lung biopsy revealed adenocarcinoma and a left upper lobectomy (ND2a-1) was performed. The tumor consisted mainly of tall columnar clear cells, and no morules were found. Immunohistochemically, the tumor was positive for alpha-fetoprotein (AFP) and p53. Accordingly, we made the histological diagnosis of high-grade fetal adenocarcinoma of the lung, pT2N0M0, stage IB. The patient was not received adjuvant therapy and has been doing well without any tumor recurrence for 3 months postoperatively.