Clonal spread of antimicrobial-resistant Escherichia coli isolates among pups in two kennels

Although the dog breeding industry is common in many countries, the presence of antimicrobial resistant bacteria among pups in kennels has been infrequently investigated. This study was conducted to better understand the epidemiology of antimicrobial-resistant Escherichia coli isolates from kennel pups not treated with antimicrobials. We investigated susceptibilities to 11 antimicrobials, and prevalence of extended-spectrum β-lactamase (ESBL) in 86 faecal E. coli isolates from 43 pups in two kennels. Genetic relatedness among all isolates was assessed using pulsed-field gel electrophoresis (PFGE). Susceptibility tests revealed that 76% of the isolates were resistant to one or more of tested antimicrobials, with resistance to dihydrostreptomycin most frequently encountered (66.3%) followed by ampicillin (60.5%), trimethoprim-sulfamethoxazole (41.9%), oxytetracycline (26.7%), and chloramphenicol (26.7%). Multidrug resistance, defined as resistance against two or more classes of antimicrobials, was observed in 52 (60.5%) isolates. Three pups in one kennel harboured SHV-12 ESBL-producing isolates. A comparison between the two kennels showed that frequencies of resistance against seven antimicrobials and the variation in resistant phenotypes differed significantly. Analysis by PFGE revealed that clone sharing rates among pups of the same litters were not significantly different in both kennels (64.0% vs. 88.9%), whereas the rates among pups from different litters were significantly different between the two kennels (72.0% vs. 33.3%, P < 0.05). The pups in the two kennels had antimicrobial-resistant E. coli clones, including multidrug-resistant and ESBL-producing clones. It is likely that resistant and susceptible bacteria can clonally spread among the same and/or different litters thus affecting the resistance prevalence

Improvement Effect of 5-Aminolevulinic Acid on Hyperlipidemia in Miniature Schnauzer Dogs: An Open Study in 5 Cases of One Pedigree

This is the first study to examine the long-term effect of 5-aminolevulinic acid mainly on serum lipoproteins in dogs with hyperlipidemia. We studied 5 Miniature Schnauzer cases whose fasting serum total triglyceride and very-low-density lipoprotein of triglyceride levels were extremely high (635 ± 116 and 520 ± 92 mg/dL, respectively). Although the total cholesterol values were normal, the very-low-density lipoprotein of cholesterol level was high (49 ± 7 mg/dL). Each dog received a 5-aminolevulinic acid supplement (5 mg/day) orally for 6 months. The mean values of total triglyceride, verylow- density lipoprotein of both triglyceride and cholesterol decreased significantly after the treatment period (319 ± 29, 245 ± 18, and 27 ± 2 mg/dL, respectively, P < 0.05). Our present results may present evidence that 5-ALA administration contributes to improvement of hyperlipidemia in Miniature Schnauzer

Pharmacokinetic–pharmacodynamic analysis of cefmetazole against extended-spectrum β-lactamase-producing Enterobacteriaceae in dogs using Monte Carlo Simulation

IntroductionThe spread of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is a serious concern in companion animal medicine owing to their ability to develop multidrug resistance. Cefmetazole (CMZ) is a candidate drug for treating ESBL-E infections; however, its regimen in dogs has not been established. In this study, we investigated the pharmacokinetic (PK) indices of CMZ in dogs and performed PK–pharmacodynamic (PD) analyses using Monte Carlo Simulation (MCS).MethodsIn total, six healthy dogs received an intravenous bolus dose of CMZ (40 mg/kg body weight). Serum CMZ concentrations were evaluated using liquid chromatography–mass spectrometry, and PK indices were determined based on non-compartmental analysis. The PK–PD cut-off (COPD) values were calculated as the highest minimum inhibitory concentration (MIC) that achieved ≥90% probability of target attainment for a target value of unbounded drug concentration exceeding 40% of the dosing interval. The cumulative fraction of response (CFR) was calculated based on the MIC distribution of wild-type ESBL-E from companion animals.ResultsThe area under the concentration–time curve and elimination half-time were 103.36 ± 7.49 mg·h/L and 0.84 ± 0.07 h, respectively. MCS analysis revealed that COPD values for regimens of 40 mg/kg q12, q8h, and q6h were ≤ 0.5, ≤2, and ≤ 4 μg/mL, respectively. A regimen of 40 mg/kg q6h was estimated to achieve a CFR of 80–90% for Escherichia coli and Klebsiella pneumoniae. By contrast, all regimens exhibited a CFR of ≤70% for Proteus mirabilis and Enterobacter cloacae.DiscussionWe conclude that CMZ at 40 mg/kg q6h could be a viable treatment regimen for dogs infected with ESBL-producing Escherichia coli and Klebsiella pneumoniae

Myxedema coma accompanied by sick sinus syndrome and hypoventilation: A case report

Myxedema coma is an emergency presentation of hypothyroidism, and cardiopulmonary manifestations of the disease are related to a high mortality rate. We herein report a case of myxedema coma accompanied by sick sinus syndrome requiring temporary cardiac pacing and hypercapnic respiratory failure in an 87-year-old woman. This case is unique because both of the cardiac and pulmonary manifestations were reversible and successfully treated with thyroid hormone replacement. Our case indicates that early detection of the condition and administration of levothyroxine are essential to improve the life-threatening condition and avoid invasive treatment such as permanent pacemaker implantation or intubation

Effects of employment of distinct strategies to capture antibody on antibody delivery into cultured cells

The characteristics of antibody delivery into cultured HeLa cells were examined by using two delivery systems. Both systems used a cell-penetrating peptide as a tool for intrusion of an antibody into the cells, but either a “protein A derivative” or “hydrophobic motif” was employed to capture the antibody. When we examined the uptake of the Alexa Fluor-labeled antibody by use of these two systems, both systems were found to effectively deliver the antibody into the cultured cells. However, when we compared the amount of antibody delivered by these systems with the amount of transferrin uptake, the former was 10 times smaller than the latter. The lower efficiency of antibody delivery than transferrin uptake seemed to be attributable to the involvement of the antibody delivery reagent, which failed to catch the antibody molecule. This interpretation was validated by an experiment using a larger amount of antibody, and the amount of antibody delivered by the “protein A derivative” system under this condition was determined to be 13 ng proteins/105 cells. The antibody delivery achieved by the “protein A derivative” or “hydrophobic motif” showed two differences, i.e., a difference in intracellular distribution of the delivered antibody molecules and a difference in the fluorescence spectrum observed with cellular lysates. Possible reasons for these differences between the two delivery systems are discussed

日本人の免疫性血栓性血小板減少性紫斑病患者における不十分な血漿交換は致死的な転帰と強く相関する

Plasma exchange (PEX) using fresh frozen plasma has considerably reduced the mortality rate in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, some patients still do not survive even with treatment, but little information is available regarding which treatment these patients received. This study was conducted to obtain this information in 240 patients who met the current iTTP diagnostic criteria and completed at least 30 days of follow-up except for deceased cases. These patients were divided into three groups: survivors (n = 195), TTP-related deaths (n = 32), and other cause of death (n = 13). In the TTP-related death group, 26 of 32 patients experienced sudden death, mostly following radical hypotension and bradycardia. The median follow-up time after admission was 5.0 days, and the median number of PEX sessions was 2.5. Nine patients underwent autopsy and had cardiac microvascular thrombi in arterioles. Levels of lactate dehydrogenase, total bilirubin, serum creatinine, and D-dimer were significantly higher in the TTP-related death group than in the survivors group. Frequent PEX (> 20 sessions) was not associated with TTP-related death. In the acute phase of iTTP, patients with substantial organ damage caused by microthrombi have a greater mortality risk, even after just a few PEX sessions.博士（医学）・乙第1518号・令和3年12月21日© Japanese Society of Hematology 2021.The version of record of this article, first published in International journal of hematology, is available online at Publisher’s website: http://dx.doi.org/10.1007/s12185-021-03197-5.発行元が定める登録猶予期間終了の後、本文を登録予定（2022.10

Secondary outflow driven by the protostar Ser-emb 15 in Serpens

We present the detection of a secondary outflow associated with a Class I source, Ser-emb 15, in the Serpens Molecular Cloud. We reveal two pairs of molecular outflows consisting of three lobes, namely primary and secondary outflows, using ALMA 12CO and SiO line observations at a resolution of 318 au. The secondary outflow is elongated approximately perpendicular to the axis of the primary outflow in the plane of the sky. We also identify two compact structures, Sources A and B, within an extended structure associated with Ser-emb 15 in the 1.3 mm continuum emission at a resolution of 40 au. The projected sizes of Sources A and B are 137 au and 60 au, respectively. Assuming a dust temperature of 20 K, we estimate the dust mass to be 0.0024 Msun for Source A and 0.00033 Msun for Source B. C18O line data imply the existence of rotational motion around the extended structure, however, cannot resolve rotational motion in Source A and/or B, due to insufficient angular and frequency resolutions. Therefore, we cannot conclude whether Ser-emb 15 is a single or binary system. Thus, either Source A or B could drive the secondary outflow. We discuss two scenarios to explain the driving mechanism of the primary and secondary outflows: the Ser-emb 15 system is (1) a binary system composed of Source A and B or (2) a single star system composed of only Source A. In either case, the system could be a suitable target for investigating the disk and/or binary formation processes in complicated environments. Detecting these outflows should contribute to understanding complex star-forming environments, which may be common in the star-formation processes.Comment: 21 pages, 10 figures, Accepted for publication in the Astrophysical Journa

Formation of High-Mass stars in an isolated environment in the Large Magellanic Cloud

The aim of this study is to characterize the distribution and basic properties of the natal gas associated with high-mass young stellar objects (YSOs) in isolated environments in the Large Magellanic Cloud (LMC). High-mass stars usually form in Giant Molecular Clouds (GMCs) as part of a young stellar cluster, but some OB stars are observed far from GMCs. By examining the spatial coincidence between the high-mass YSOs and 12CO (J = 1-0) emission detected by NANTEN and Mopra observations, we selected ten high-mass YSOs that are located away from any of the NANTEN clouds but are detected by the Mopra pointed observations. The ALMA observations revealed that a compact molecular cloud whose mass is a few thousand solar masses or smaller is associated with the high-mass YSOs, which indicates that these compact clouds are the sites of high-mass star formation. The high-density and high-temperature throughout the clouds are explained by the severe photodissociation of CO due to the lower metallicity than in the Galaxy. The star formation efficiency ranges from several to as high as ~ 40%, indicating efficient star formation in these environments. The enhanced turbulence may be a cause of the efficient star formation therein, as judged from the gas velocity information and the association with the lower density gas.Comment: 31 pages, 14 figures, PASJ accepted for publicatio