Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain.

Botulinum neurotoxin type A (BoNT/A) induces muscle atrophy by cleaving synaptosomal-associated protein 25. Thus, BoNT/A has been actively utilized for the treatment of masseter and gastrocnemius hypertrophy. In this study, INI101 toxin was newly identified from the CCUG 7968 strain, and its therapeutic efficacy was evaluated both in vitro and in vivo. The INI101 toxin showed identical genetic sequence, amino acid sequence, and protein subunit composition to BoNT/A produced from strain Hall A. Electromyography (EMG), and immunofluorescence staining demonstrated that INI101 (at 2 ~ 8 U/rat) effectively blocked the neuromuscular junction with no toxicity in a rat model. The EMG results showed INI101 toxin-induced weight loss and volume reduction of the gastrocnemius, similar to the effects of Botox® (BTX). Histological and immunofluorescence staining was consistent with this EMG result, showing that INI101 toxin caused muscle fiber reduction in the gastrocnemius. Notably, INI101 toxin diffused less into adjacent muscle tissue than BTX, indicating that INI101 toxin may reduce potential side effects due to diffusion into normal tissues. INI101 toxin isolated from the novel strain CCUG 7968 is a newly identified meaningful biopharmaceutical comparable to the conventional BoNT/A in the medical field. KEY POINTS: • Botulinum neurotoxin type A (BoNT/A, INI101) was identified from the CCUG 7968 strain. • INI101 toxin showed similar safety and therapeutic efficacy comparable to conventional BoNT/A both in vitro and in vivo. • INI101 toxin is a meaningful biopharmaceutical comparable to the conventional BoNT/A in the medical field.

Antitussive effect of a magnesium infusion during anesthetic emergence in patients with double-lumen endotracheal tube: a randomized controlled trial.

BACKGROUND: A double-lumen endotracheal tube (DLT) inserted into the bronchus can stimulate the respiratory tracts, causing coughing. Opioids have been introduced to prevent emergence cough. However, the administration of a significant opioid dose at the end of surgery may result in undesirable events. Magnesium, common intracellular ion, suppress bronchial smooth muscle contraction and have antitussive effect. We investigated the antitussive effects of a magnesium infusion during anesthetic emergence in patients who underwent thoracic surgery requiring one-lung ventilation (OLV) anesthesia with a DLT. METHODS: One-hundred forty patients undergoing OLV anesthesia with a DLT were enrolled in this prospective, randomized double-blinded trial. In combination with a low dose of remifentanil, patients were randomly allocated to receive either magnesium sulphate (infusion of 15 mg/kg/hour after a single bolus of 30 mg/kg) or normal saline during the operation and emergence. Primary outcomes were the severity and incidence of cough during emergence. RESULTS: The severity of cough was assessed by the cough severity grading score: 0, no cough; 1, single cough; 2, cough persistence <5 seconds; 3, cough persistence ≥5 seconds. There was a significant difference in the severity score of cough between the groups [median (IQR): 2 (0 to 3) in control group vs. 0 (0 to 1) in magnesium group, P=0.003]. However, there was no significant difference in the overall incidence of cough between both groups [42 (64.6%) in control group vs. 31 (47.7%) in magnesium group, P=0.077]. CONCLUSIONS: Magnesium attenuated the severity of cough during emergence after OLV anesthesia using a DLT without adverse events.

Time to tracheal intubation over a fibreoptic bronchoscope using a silicone left double-lumen endobronchial tube versus polyvinyl chloride single-lumen tube with bronchial blocker: a randomized controlled non-inferiority trial.

BACKGROUND: Direct insertion of a double-lumen endobronchial tube (DLT) over a fibreoptic bronchoscope (FOB) is considered more difficult and traumatic than that of a single-lumen tube (SLT). We hypothesized that time to intubation over an FOB using a silicone left DLT would be non-inferior to that using a polyvinyl chloride (PVC) SLT. METHODS: Eighty patients were enrolled in this open-label, randomized controlled, non-inferiority trial. Patients were randomly allocated to fibreoptic tracheal intubation with either a silicone DLT or PVC SLT (DLT and SLT groups, respectively). Time to tracheal intubation [time to insertion of FOB plus railroading (advancement over the FOB) time]; total time for correct tube and bronchial blocker positioning; difficulty of railroading; and the incidence of sore throat, swallowing difficulty, and hoarseness were compared between groups. RESULTS: The median time to intubation over the FOB was 20 s in the DLT group and 23 s in the SLT group. The upper limit of the confidence interval of this difference was below the non-inferiority margin of 10 s (median difference: -2 s; 95% confidence interval: -4 to 0 s). Railroading time was significantly shorter in the DLT group than in the SLT group (median time: 10 vs. 11 s; median difference: -1 s; 95% confidence interval: -3 to 0 s; P=0.03). Railroading over the FOB (rated on a four-point scale) was less difficult in the DLT group than in the SLT group (P<0.01). CONCLUSIONS: Tracheal intubation using an FOB can be achieved at least as fast using the silicone DLT as using the PVC SLT. The silicone DLT exhibited superior railroading performance to the PVC SLT.

Comparison of the McGrath videolaryngoscope and the Macintosh laryngoscope for double lumen endobronchial tube intubation in patients with manual in-line stabilization: A randomized controlled trial.

BACKGROUND: Double lumen endobronchial tube (DLT) intubation is commonly used for one-lung ventilation in thoracic surgery. However, because of its large size and shape, it is difficult to perform intubation compared with a single lumen tube. The aim of this randomized controlled trial was to determine whether the McGrath videolaryngoscope has any advantage over the direct Macintosh laryngoscope for DLT intubation in patients with a simulated difficult airway. METHODS: Forty-four patients (19-60 years of age); scheduled to undergo general anesthesia with one-lung ventilation were assigned to 1 of 2 groups: DLT intubation with the McGrath videolaryngoscope (ML group [n = 22]); or conventional Macintosh laryngoscope (DL group [n = 22]). After manual in-line stabilization was applied as a way of simulating a difficult airway, the time required for intubation and the quality of glottic view were evaluated. RESULTS: The time to successful intubation was not different between the 2 groups (ML group, 45 s [interquartile range, 38-52 s] versus DL group, 54 s [45-59 s]; P = .089). The McGrath videolaryngoscope, however, provided a significantly better glottic view. Modified Cormack and Lehane grade was better (P < .001), and the percentage of glottis opening score was higher in the ML group (P < .001). Overall intubation difficulty scale score was lower in the ML group (1 [0-2]) versus the DL group (3 [2-4]) (P < .001). CONCLUSION: The McGrath videolaryngoscope improved glottic view and resulted in lower overall intubation difficulty scale score in patients with in-line stabilization.

Use of bacteriophage for biological control of Salmonella Enteritidis infection in chicken.

Bacteriophage ΦCJ07 with broad host ranges for Salmonella strains isolated from sewage effluent were used to reduce Salmonella Enteritidis (SE) infection in chickens. One-day-old chicks challenged with 5×10(7) colony-forming units/bird of SE were cohabitated with contact chicks and treated with three concentrations (10(5), 10(7) and 10(9) plaque forming units (PFU)/g) of bacteriophage prepared as a feed additive for 21days after challenge. Salmonella in the intestine was quantified and environmental contamination level was examined at 1, 2 and 3weeks after challenge. All treatments reduced intestinal SE colonization in challenged and contact chickens and reduced the environmental contamination level, but the reductions produced by 10(7) and 10(9)PFU/g of bacteriophage were significant (P<0.05) as compared with untreated controls. In addition, seven out of 10 (70%) contact chickens treated with 10(9)PFU/g of bacteriophage had no detectable intestinal Salmonella at 3weeks after treatment, suggesting that bacteriophage therapy significantly prevented the horizontal transmission of SE. These results provide important insights into preventive and control strategies against SE infection in poultry and indicate that the use of bacteriophage could reduce the incidence of Salmonella food poisoning.

Efficacy of bacteriophage therapy on horizontal transmission of Salmonella gallinarum on commercial layer chickens.

A Salmonella Gallinarum (SG)-specific bacteriophage isolated from sewage effluent was used to prevent horizontal transmission of SG in commercial layer chickens. Six-week-old chickens, each challenged with 5 x 10(8) colony-forming units of SG, cohabited with contact chickens treated with 10(6) plaque-forming units/kg of bacteriophage, prepared in feed additives, for 7 days before, and 21 days after challenge with SG. Mortality was observed for 3 wk after challenge and SG was periodically reisolated from the liver, spleen, and cecum of chickens. SG re-isolation from organs was decreased and a significant (P < 0.05) reduction in mortality was observed in contact chickens treated with the bacteriophage, as compared to untreated contact chickens, indicating that bacteriophage administration in feed additives significantly prevented the horizontal transmission of SG. These results provide important insights into prevention and control strategies against SG infection and suggest that the use of bacteriophages may be a novel, safe, and effectively plausible alternative to antibiotics for the prevention of SG infection in poultry.

An emerging recombinant cluster of nephropathogenic strains of avian infectious bronchitis virus in Korea.

The infectious bronchitis virus (IBV) is continuously evolving through point mutation and recombination of their genome, subsequently the emergence of IBV variants complicates disease control. The objective of this study was to investigate genetic characterization of new IBV variants isolated from commercial chicken flocks in Korea collected between 2005 and 2010. Phylogenetic analysis revealed that all new IBV isolates belonged to Korean group II (K-II), which included the nephropathogenic IBV strains. However, the isolates formed a new gene cluster that was distinguished from the two distinct K-II subgroups (KM91-like and QX-like). Recombination events were identified in the S1 gene, with their putative parental strains being the KM91-like or QX-like subgroup. In addition, two crossover sites were observed in the S1 gene of IBV isolates. These results suggest that natural genetic recombination between heterologous strains classified into different genetic groups has occurred and may have caused the emergence of new IBV strains. This finding provides important information on IBV evolution and is essential for the effective control of IB in Korea.

Identification and virulence characterization of fowl adenoviruses in Korea.

Since 2007, 55 adenovirus strains have been isolated from commercial chicken flocks in Korea and have been identified and the pathogenicity of these isolates was confirmed in specific-pathogen-free chickens of different age. Based on sequencing analysis of the hexon gene, 55 FAdV isolates were genetically related to the IBH-2A strain of FAdV3 (4 isolates, 99.2% to 100%), the KR5 strain of FAdV4 (22 isolates, 97.9% to 99.2%), the 764 strain of FAdV9 (11 isolates, 99.1% to 99.3%), and the 1047 strain of FAdV11 (18 isolates, > 99%). Experimental infections with four serotypes of FAdV resulted in high mortality of 18-day-old chicken embryos and 1-day-old chicks with marked liver necrosis similar to those observed in the natural outbreaks. Notably, specific hydropericardium was observed in chicks challenged with the K531 strain (serotype 4). However, 3-wk-old chickens challenged with FAdVs, regardless of serotype, did not show any clinical signs or mortality except histologic lesions of focal hepatocytic necrosis with mild lymphocytic infiltration. The results indicate that four FAdV serotypes (3, 4, 9, and 11) are the dominant serotypes of FAdVs in the Korea and are pathogenic enough to cause clinical disease in young chicks. The present investigation provides important information on the epidemiology and pathogenesis of FAdVs and highlights the importance of control strategies against FAdV infection in Korea.