150 kDa glycoprotein isolated from Solanum nigrum Linne enhances activities of detoxicant enzymes and lowers plasmic cholesterol in mouse.

This study was carried out to investigate the modulation of detoxicant enzyme activity and plasma lipidemic levels by 150 kDa glycoprotein isolated from Solanum nigrum Linne (SNL), which has been used as a hepatoprotective and anticancer agent in folk medicine. Our results in this study showed that SNL glycoprotein has a band with 150 kDa on the 10% sodium dodecyl sulfate polyacrylamide gel, and that it has a strong scavenging activity against lipid peroxyl radicals. We also evaluated the lipidemic levels of SNL glycoprotein, based on lipoproteins and activities of detoxicant enzymes in treatment with Triton WR-1339 or corn oil in vivo. When mice were treated with either Triton WR-1339 or corn oil in the absence of SNL glycoprotein, the number of plasma lipoproteins [triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL)] increased. However, when the mice were treated with either Triton WR-1339 or corn oil in the presence of SNL glycoprotein, the plasma lipoprotein levels (TG, TC and LDL) were significantly reduced. Similar results of SNL glycoprotein treatment were also produced in the activities of detoxicant enzymes. Namely, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were remarkably increased after treatment with SNL glycoprotein. In addition, the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was reduced by SNL glycoprotein in cholestyramine-treated mice. For example, we found that it inhibits the activity of cholestyramine-induced hepatic HMG-CoA reductase at 40 microg head body weight g(-1) SNL glycoprotein. Collectively, these results pointed out that SNL glycoprotein can enhance the activities of detoxicant enzymes and bring about the inhibition of HMG-CoA reductase activity in vivo. Therefore, we speculate that SNL glycoprotein can be used as a cholesterol-lowering agent even at low concentrations.     

Postero-medio-anterior approach of the ankle for the pilon fracture

A good view of the operative field is important for better reduction and fixation in surgical treatment of fractures. The exposure of the ankle joint for the pilon fracture is commonly through the anterior approach, or combined with the medical approach. But sometimes it is still difficult to have complete viewing of the articular surface and to apply internal fixation by that approach. In recent years, we developed a "postero-medio-anterior" approach of the ankle joint by one incision. This approach provides an excellent exposure of the anterior, medial and posterior aspects of the ankle joint with a clear view of the articular surface. In our 45 cases of pilon fracture during 1991 to 1995, there was no incisional injury to the neurovascular bundle. Superficial wound edge necrosis was noted in two cases which healed later without further procedure. Therefore, we recommend this approach as a simple and reliable incision for open reduction of pilon fractures.     

Prolonged extracorporeal membrane oxygenation support for acute respiratory distress syndrome.

When all conventional treatments for respiratory failure in patients with acute respiratory distress syndrome (ARDS) have failed, extracorporeal membrane oxygenation (ECMO) can provide a chance of survival in these desperately ill patients. A 49-year-old male patient developed septic shock and progressive ARDS after liver abscess drainage. Venovenous ECMO was given due to refractory respiratory failure on postoperative day 6. Initially, two heparin-binding hollow-fiber microporous membrane oxygenators in parallel were used in the ECMO circuit. Twenty-two oxygenators were changed in the first 22 days of ECMO support because of plasma leak in the oxygenators. Each oxygenator had an average life of 48 hours. Thereafter, a single silicone membrane oxygenator was used in the ECMO circuit, which did not require change during the remaining 596 hours of ECMO. The patient's tidal volume was only 90 mL in the nadir and less than 300 mL for 26 days during the ECMO course. The patient required ECMO support for 48 days and survived despite complications, including septic shock, ARDS, acute renal failure, drug-induced leukopenia, and multiple internal bleeding. This patient received an unusually long duration of ECMO support. However, he survived, recovered well, and was in New York Heart Association functional class I-II, with a forced expiratory volume in 1 second of 81% of the predicted level 18 months later. In conclusion, ECMO can provide a chance of survival for patients with refractory ARDS. The reversibility of lung function is possible in ARDS patients regardless of the severity of lung dysfunction at the time of treatment.     

Jejuketomycins A and B,polyketide glycosides with cancer cell migration inhibitory activity from Streptomyces sp. KCB15JA151

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data. Compounds 1 and 2 possess an unusual 6/6/8 tricyclic ring system. Biological evaluation with the wound healing assay and time-lapse cell tracking analysis revealed that compounds 1 and 2 have significant inhibitory activities against cancer cell migration with low cytotoxicity.

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151.     

Cardiovascular Medication Use and Risk of Acute Exacerbation in Patients With Asthma-COPD Overlap (CVACO Study)

PurposeCurrent clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).MethodsWe conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE.ResultsThe final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44–0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11–0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45–0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30–0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38–0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE.ConclusionsARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO.