Prevalence, resistance phenotypes, and fluoroquinolone resistance genes of Salmonella isolates from raw milk of healthy dairy cows in Henan province, China.

OBJECTIVE: Salmonella isolates have been discovered in many regions of the world. We investigated the prevalence and resistance of Salmonella isolates in raw milk of healthy dairy cows on farms in different regions of Henan Province, China. MATERIALS AND METHODS: From July 2020 to November 2021, 422 raw milk samples were collected. The minimum inhibitory concentrations (MICs) of 16 antimicrobial agents against 89 Salmonella strains detected from the raw milk samples were determined using the broth microdilution method, and the resistance genes for fluoroquinolones were identified using polymerase chain reaction. RESULTS: Eighty-nine (21.09%) Salmonella isolates were recovered from 422 raw milk samples. The Salmonella strains exhibited high resistance to amoxicillin (100.00%), tylosin (95.50%), and lincomycin (95.50%). Additionally, tigecycline showed good activity against Salmonella, with an MIC50 of 0.25 µg/mL. All Salmonella isolates showed multidrug resistance (MDR), and >50% of the strains showed resistance to more than six antimicrobials. The strains from Jiaozuo exhibited 100% resistance to amoxicillin, terramycin, tylosin, and lincomycin. Two efflux pump genes, oqxA and oqxB, had the highest carrying rates of 66.29% and 64.04%, respectively. Additionally, the carrying rates of oqxA and oqxB were high in Shangqiu, Zhengzhou, and Jiaozuo. The carrying rates of aac(6')-Ib-cr in Shangqiu and Zhengzhou were 33.33% and 38.46%, respectively. CONCLUSIONS: This study revealed a high prevalence of Salmonella isolates obtained from raw milk of healthy dairy cows in different regions of Henan Province, China. The Salmonella strains exhibited various degrees of MDR. Salmonella can be transmitted to humans via consumption of contaminated raw milk; thus, the presence of resistance genes poses a potential threat to public health, highlighting the need for vigilant monitoring of Salmonella isolates.

[Clinical significance of minimal residual disease in patients with Ph-negative precursor B-acute lymphoblastic leukemia].

Objective: To explore the predictive value of minimal residual disease (MRD) level in Ph-negative precursor B-acute lymphoblastic leukemia (ALL) patients. Methods: De novo 193 Ph-negative B-ALL patients from Sep 2010 to Nov 2017 were involved in the study. The patients' MRD evaluation which can be performed by multiparametric flow cytometry (MFC) after 1 month, 3-month, 6-month treatment. Relapse free survival (RFS) and overall survival (OS) were compared in patients with different MRD level. Results: The median follow-up was 22 months. All patients was evaluated at 497 MRD level. Patients who reach the good MRD level at 1 month (<0.1% or ≥0.1%), 3-month (negative or positive), 6-month (negative or positive) had a significantly higher probability of estimated RFS (74.5% vs 29.9%; 75.6% vs 29.7%; 74.6% vs 11.6%) and of estimated OS (67.5% vs 30.3%; 71.6% vs 27.8%; 74.0% vs 15.7%). Patients who reach the MRD negative at all 3 times had a significantly higher probability of estimated RFS (80.5% vs 30.5%) and better estimated OS (77.1% vs 29.4%) compared to patients with at least MRD failure in one time (P<0.001). Multivariable analysis showed MRD level at 3-month was an independent prognostic factor for DFS and OS. Conclusion: MRD is an important prognosis factor for Ph-negative B- ALL patients.

Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol.

BACKGROUND AND PURPOSE: Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol. EXPERIMENTAL APPROACH: Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg(-1) ·day(-1), i.p.) and metoprolol (20 mg·kg(-1) ·day(-1), p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling-related proteins were evaluated. KEY RESULTS: Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-κB-light-chain-enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth-associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol. CONCLUSIONS AND IMPLICATIONS: Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy.

Inhibitory effect of interferon and tumor necrosis factor on human luteal function in vitro.

OBJECTIVE: To investigate whether immunological mechanisms may be involved in human luteal function. DESIGN: The effects of the cytokines, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on steroidogenesis by human luteal cells were examined in vitro. The dispersed human luteal cells, obtained from a total of 17 women at laparotomy, were cultured separately in the presence or absence of human chorionic gonadotropin (hCG) and IFNs/TNF-alpha with the medium being replaced at 48 hours. The medium was collected at 48 and 96 hours for steroid assays. RESULTS: The IFN-alpha had no significant effect on the production of estradiol or progesterone (P), whereas a dose-related inhibition of basal, as well as hCG-stimulated P formation, was observed after the addition of IFN-gamma (10 to 1,000 U/mL). Progesterone production was inhibited to about 45% of the control at 48 hours and even lower at 96 hours (n = 6, P < 0.001). The combination of IFN-gamma and low doses of TNF-alpha induced a further significant inhibition, whereas there was no effect of TNF-alpha alone. This inhibitory effect of IFN-gamma could be completely neutralized with a monoclonal antibody to IFN-gamma. Incubation with the antibody alone increased the production of P from luteal cells in culture, suggesting a local tonic inhibitory action of endogenous IFN-gamma. CONCLUSION: Interferon-gamma and TNF-alpha, whose function classically is known as antiviral, also may play a role in human luteal regression by inhibiting luteal P production.

Syntheses of argininal semicarbazone containing peptides and their applications in the affinity chromatography of serine proteinases.

Eight argininal semicarbazone containing peptides prepared by liquid phase synthesis were all found to be reversible inhibitors of model serine proteinases including trypsin and plasma kallikrein (PK). Among the peptides tested, those having a Lys residue at position P2 displayed the maximum binding potency towards PK. One of the peptides, Leu-enkephalin-argininal semicarbazone, a comparatively weak inhibitor, was chosen in order to develop an affinity-based purification protocol for PK. The affinity column was prepared by covalent attachment of the NH2-terminal moiety of the peptidyl semicarbazone to a solid-phase matrix bearing a spacer group. For efficient binding of PK, it was found necessary to optimize parameters like the concentration of inhibitor linked to the solid matrix, the ionic strength of the buffer used, the temperature and the pH. The majority of the bound enzyme could be recovered following elution with guanidine hydrochloride or benzamidine hydrochloride in a high salt buffer at pH 6.0. The usefulness of the affinity procedure towards the purification of other serine proteinases is also discussed.