Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy.

BACKGROUND: Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients. AIM: To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy. METHODS: Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR. FINDINGS: Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT-PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room. CONCLUSION: Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats.

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.

Anti-tumor promoting potential of naturally occurring diarylheptanoids structurally related to curcumin.

In recent years, there have been considerable efforts to search for naturally occurring substances for intervention of carcinogenesis. Many components from medicinal or dietary plants have been identified to possess potential chemopreventive properties. For instance, curcumin, a yellow colouring agent from turmeric (Curcuma longa Linn., Zingiberaceae) has been shown to inhibit tumor formation in diverse animal models. Alpinia oxyphylla Miquel that also belongs to ginger family has been used in oriental herbal medicine. In the present work, we have evaluated the anti-tumor promoting potential of yakuchinone A (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenyl-3-heptanone) and yakuchinone B (1-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-1-en-3-one), major pungent ingredients of A. oxyphylla. Thus, topical application of yakuchinone A or B significantly suppressed TPA-induced epidermal ornithine decarboxylase activity. They also reduced TPA-stimulated production of tumor necrosis factor-alpha in cultured human promyelocytic leukemia (HL-60) cells. Both compounds blunted the TPA-induced superoxide generation in differentiated HL-60 cells in a concentration-related manner and also inhibited lipid peroxidation in rat brain homogenates. Furthermore, yakuchinone A and yakuchinone B nullified the activation of the activator protein-1 (AP-1) in immortalized mouse fibroblast cells in culture. These findings indicate that pungent diarylheptanoids from A. oxyphylla have anti-tumor promotional properties that can contribute to their chemopreventive potential.

Dopaminergic influences on the P300 abnormality in Parkinson's disease.

This study was designed to evaluate the contribution of central dopaminergic mechanisms to the P300 event-related potential (P300) abnormality in Parkinson's disease. We measured the P300 in 37 non-demented patients with Parkinson's disease (19 de novo and 18 levodopa-treated) and 15 age-matched healthy volunteers. The P300 measurement was repeated in 14 de novo patients, after 6-12 months levodopa therapy. The severity of parkinsonian symptom was assessed using the UPDRS-motor scale. De novo patients showed prolonged P300 latency compared with levodopa-treated patients, as well as healthy volunteers. The levodopa therapy for 6-12 months significantly shortened the P300 latency and reduced the UPDRS-motor examination score in de novo patients. However, the percent changes in the P300 latency were not correlated with those in the UPDRS-motor examination score. These results indicate that the central dopaminergic mechanisms apart from those responsible for motor symptoms, may contribute to the P300 abnormality in Parkinson's disease.

Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients.

Plasma concentrations and the degree of neuromuscular blockade after a 2-min infusion of 0.1 mg/kg of vecuronium bromide or pancuronium bromide (equipotent doses) were studied in 12 gynecologic patients. The plasma concentrations of both drugs declined in a triphasic manner. The difference between the intercepts and rate constants of the two drugs was not significant. Vecuronium was removed faster from the plasma than pancuronium; this was reflected in a significantly larger plasma clearance rate for vecuronium (4 ml X min-1 X kg-1 vs 1.1 ml X min-1 X kg-1 for pancuronium). The effective plasma concentrations at 50% recovery of the twitch height were 0.11 +/- 0.02 (vecuronium) and 0.2 +/- 0.03 microgram/ml (pancuronium). The disposition kinetics were adequately described by a three-compartment model. An effect compartment was added to the model to correlate the neuromuscular effects and plasma concentrations of both drugs. The ratio between concentrations of vecuronium and pancuronium in the effect compartment at 50% twitch height was 0.83. In spite of its greater potency, vecuronium has a shorter duration of action than pancuronium.

Disposition and urinary excretion of vecuronium bromide in anesthetized patients with normal renal function or renal failure.

The effect and plasma concentrations of vecuronium bromide were measured in normal patients after an intravenous dose of 50, 100, or 150 micrograms/kg and in patients with renal failure after 50 or 100 micrograms/kg. Urinary excretion of vecuronium was studied in normal patients after the 150 micrograms/kg dose. Pharmacokinetic parameters of patients with or without renal failure were similar. No metabolites of vecuronium were found in the plasma. Twenty percent of vecuronium was excreted unchanged in the urine; 5% as the 3-hydroxy derivative. No other metabolites of vecuronium were found in the urine. Increasing doses of vecuronium shortened the onset, but prolonged the duration of action and the recovery rate, to a similar extent in patients with or without renal failure. It was concluded that the disposition of vecuronium was best described by a three compartment model. Both the disposition and the effect of vecuronium are only marginally disturbed by renal failure.

Clinical pharmacology of vecuronium and atracurium.

Vecuronium and atracurium provide addition flexibility to the clinician using neuromuscular blocking drugs. The shorter duration of action, lack of significant cardiovascular effects, and the lack of dependence on the kidney for elimination provide clinical advantages over, or alternatives to, currently available nondepolarizing neuromuscular blocking drugs.

Clinical pharmacology of ORG NC45 (NorcuronTM): a new nondepolarizing muscle relaxant.

To determine the neuromuscular effects of a new muscle relaxant, ORG NC45 (Norcuron), a monoquaternary homologue of pancuronium, 84 ASA Class I or II patients were studied under halothane and nitrous oxide anesthesia. The ED50 (dose of muscle relaxant causing a 50% depression of twitch tension) of pancuronium and ORG NC45 was 0.022 mg/kg (r = 0.90) and 0.015 mg/kg (r =0.80), respectively, for a potency ratio of 1.5 (0.022/0.015). The duration of action (time from injection to 90% recovery of control twitch tension) was 27 +/- 5 min with ORG NC45, 0.02 mg/kg, and 65 +/- 16 min with pancuronium in an equivalent dose of 0.03 mg/kg. The increase in duration of neuromuscular blockade from repetitive doses was greater with pancuronium than with ORG NC45. Reversal of an ORG NC45 neuromuscular blockade was accomplished with doses of neostigmine slightly less than those required for pancuronium. Under thiopental-nitrous oxide anesthesia, endotracheal intubation was easily performed using ORG NC45, 0.07-0.14 mg/kg. The duration of action of ORG NC45, 0.07 mg/kg, was about one-third that of pancuronium (0.1 mg/kg). It was concluded that ORG NC45 is more potent and has a shorter duration of action with both initial and repetitive doses than does pancuronium. With these characteristics and the reported lack of cardiovascular effects, the authors believe further clinical trials are warranted.

Cardiovascular and neuromuscular effects of Org NC 45, pancuronium, metocurine, and d-tubocurarine in dogs.

We compared the cardiovascular and neuromuscular effects of Org NC 45 with those of pancuronium, metocurine, and d-tubocurarine in six dogs anesthetized with halothane. The ED90 (dose of drug which produced a 90% depression of twitch tension) of Org NC 45, pancuronium, metocurine, and d-tubocurarine was 14 +/- 3, 22 +/- 3, 63 +/- 19, and 130 +/- 19 micrograms/kg, respectively. All subsequent neuromuscular and cardiovascular effects were determined from a dose equal to 3 times the ED90 of muscle relaxant. Org NC 45, pancuronium, metocurine, and d-tubocurarine produced a neuromuscular blockade with a during (time from relaxant administration until recovery 50% of the original twitch tension) of 42 +/- 2, 108 +/- 10, 109 +/- 21, and 100 +/- 19 minutes, respectively. Org NC 45 caused no significant cardiovascular changes. Pancuronium increased heart rate, mean arterial blood pressure, cardiac output, and pulmonary wedge pressure, and it decreased systemic vascular resistance (p less than 0.05). Although metocurine also increased heart rate and cardiac output (p less than 0.05), mean arterial blood pressure and pulmonary wedge pressure did not change. d-Tubocurarine decreased all cardiovascular parameters except heart rate which increased significantly (p less than 0.05). We conclude that Org NC 45 produces a neuromuscular blockade of shorter duration with fewer cardiovascular changes than that of pancuronium, metocurine, or d-tubocurarine.