The purpose of the present study was to evaluate the effect of diets containing Lactobacillus plantarum CJLP243 on the growth and cytokine response of weaning pigs (Sus scrofa) challenged with enterotoxigenic Escherichia coli (ETEC). In a 28-d experiment (14 d before and 14 d after challenge), a total of 108 pigs at 20 ± 1 d of age were allotted to 1 of 6 diets. These were a control diet without ETEC challenge (CON) and 5 treatment diets with ETEC challenge, including a control diet with ETEC challenge (negative control, NC); a positive control diet containing antibiotics (PC); control diet plus (10(8), 10(9), or 10(10)) cfu/kg L. plantarum CJLP243 (T1, T2, and T3, respectively). After challenge, NC showed the least ADFI, whereas PC and T3 had the greatest ADFI (P = 0.002). The ADG of PC, T2, and T3 were greater (P = 0.001) than that of CON, NC, and T1 during wk 1 to wk 2. During wk 3 to wk 4, a marked decline was seen in NC (P = 0.001) compared with CON, whereas PC and T3 showed increased ADG (P = 0.001). The overall ADG of PC and T3 were greater (P < 0.001) than the remaining groups. The PC and T3 had the greatest G:F during the second 2 wk (P = 0.002), and the overall 4-wk experimental period (P = 0.003). At 3 h after challenge, all groups except CON had greater rectal temperatures (RT; P < 0.05). The RT decreased to prechallenge temperatures at 9 h (PC and T3), 24 h (T1 and T2), and remained increased until d 7 in NC. At 7 and 14 d postinfection, the number of animals detected positive for ETEC by PCR assay was the greatest in NC; however, the PC group had the fewest ETEC-positive animals (P < 0.05), which was similar to T3. All challenged pigs, except T2, had greater concentrations of serum haptoglobin compared with CON, with the greatest concentration observed in NC (P < 0.001). Challenged pigs had increased serum concentrations of tumor necrosis factor alpha (TNF-α) 3 to 48 h postinfection, with the greatest concentration of TNF-α at 48 h observed in NC (P < 0.05). Similarly, greater (P < 0.05) serum concentrations of interferon-γ were observed for 9 h (T1 and T3), 24 h (T2 and PC), and 48 h (NC) postinfection. The serum concentration of IL-6 increased (P < 0.05) for 3 h in T3 and 24 h in NC. In conclusion, our findings suggest that L. plantarum CJLP243, at a concentration of 10(10) cfu/kg, may serve as a potential alternative to antibiotic supplementation to improve the growth and health performance of weaning pigs, especially during acute inflammation of the gut after bacterial infections.

Our previous studies showed that cigarette smokers who are exposed to wood smoke (WS) are at an increased risk for chronic bronchitis and reduced lung function. The present study was undertaken to determine the mechanisms for WS-induced adverse effects. We studied the effect of WS exposure using four cohorts of mice. C57Bl/6 mice were exposed for 4 or 12 weeks to filtered air, to 10 mg/m 3 WS for 2 h/d, to 250 mg/m 3 cigarette smoke (CS) for 6 h/d, or to CS followed by WS (CW). Inflammation was absent in the filtered air and WS groups, but enhanced by twofold in the bronchoalveolar lavage of the CW compared with CS group as measured by neutrophil numbers and levels of the neutrophil chemoattractant, keratinocytederived chemokine. The levels of the anti-inflammatory lipoxin, lipoxin A4, were reduced by threefold along with cyclo-oxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 in airway epithelial cells and PGE 2 levels in the bronchoalveolar lavage of CW compared with CS mice. We replicated, in primary human airway epithelial cells, the changes observed in mice. Immunoprecipitations showed that WS blocked the interaction of aryl hydrocarbon receptor (AHR) with AHR nuclear transporter to reduce expression of COX-2 and mPGES-1 by increasing expression of AHR repressor (AHRR). Collectively, these studies show that exposure to low concentrations of WS enhanced CS-induced inflammation by inducing AHRR expression to suppress AHR, COX-2, and mPGES-1 expression, and levels of PGE 2 and lipoxin A4. Therefore, AHRR is a potential therapeutic target for WS-associated exacerbations of CS-induced inflammation.

1.The aim of the present study was to determine the PKs of marbofloxacin in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration, the ex vivo and in vitro PK/PD indices of marbofloxacin against clinical isolates of Staphylococcus pseudintermedius, and the ex vivo AUC/MIC ratios associated with different levels of antibacterial activity. 2.After i.v. of marbofloxacin (2 mg/kg), the mean ± SEM values of AUC, t1/2β, Vss, and CL were 8.47 ± 3.51 h µg/mL, 8.08 ± 6.25 h, 2.32 ± 1.00 L/kg and 0.23 ± 0.06 L/kg/h and corresponding values after intramuscular injection were 11.37 ± 3.07 h µg/mL, 7.51 ± 3.70, 1.80 ± 0.90 L/kg and 0.17 ± 0.04 L/kg/h. After i.m. administration, a Cmax of 1.76 ± 0.09 µg/mL was achieved at Tmax of 0.47 ± 0.08 h. The ex-vivo AUC/MIC ratios required to produce bacteriostasis, bactericidal action and elimination of S. pseudintermedius were 65.03, 97.02 and 136.84 h. 3.The in vivo AUC/MIC ratios obtained after i.v. and i.m. administration of 2 mg/kg marbofloxacin (67.76 ± 1.23 and 91.18 ± 2.61) were below the ex vivo AUC/MIC ratios required for bactericidal activity and bacterial elimination (97.02 ± 9.24 2 mg/kg and 136.21 ± 7.58), suggesting that the recommended daily dosage (2 mg/kg) may not suffice to kill and eradicate S. pseudintermedius strains encountered in clinical area.

Cigarette smoke (CS)-exposed mice have been used to model airway inflammation and emphesema in humans; however, the impact of exposure duration, sex, and strain differences in susceptibility to progression of airway inflammation and to emphesema are poorly investigated. This study was designed to determine the association between inflammation and emphysema by exposing 2 strains of mice, C3H/HeN (C3H) and C57BL/6 (Bl/6), to filtered air (FA) or CS for 10, 16, or 22 weeks. Both genders and strains of CS-exposed mice developed pulmonary inflammation as characterized by cell counts in the bronchoalveolar lavage fluid (BALF) and the levels of matrix metalloproteinases (MMPs) in the BALF. CS exposure caused persistently higher number of BALF macrophages in C3H compared to BL/6 mice, while more BALF neutrophils and persistently higher MMP-2 and MMP-9 levels were observed in BL/6 mice. The mean linear intercept (Lm) increased progressively by 26%, 33%, and 55% at 10, 16, and 22 weeks, respectively, in CS-exposed C3H mice compared to the matched air controls. In BL/6 mice, although CS exposure also increased the Lm compared to FA controls, no further increase in Lm beyond the levels observed at 16 weeks of exposure was observed by 22 weeks. These findings suggest that extent of inflammation is not associated with severity of emphysema and underscores the importance of carefully selecting the mouse strains and endpoints when exploring effective treatments for emphesema.

Background –  The problem of antibacterial drug resistance is increasing worldwide, in part due to the therapeutic concentrations currently used based on the minimal inhibitory concentration (MIC) as a measure of potency are often the very concentrations required to selectively enrich the resistant mutant portion of the population. A mutant prevention concentration (MPC)‐based dosing strategy is suggested to improve the therapeutic outcome based on the MIC. Objective –  Our aim was to investigate the MPC and mechanism of resistance to various fluoroquinolones using recent Staphylococcus pseudintermedius isolates from canine pyoderma. Methods –  The broth microdilution method for MIC and a series of agar plates containing different concentrations of fluoroquinolones were inoculated with ∼1010 colony‐forming units of the bacterial culture for MPC were used. PCR was used to identify mutation in the resistant isolates. Results –  The rank order of potency based on MIC and MPC was ciprofloxacin = enrofloxacin ≥ marbofloxacin > difloxacin ≥ orbifloxacin. Integrating our data with reported pharmacokinetic data at the recommended dose ranges revealed that only high doses of ciprofloxacin, enrofloxacin and marbofloxacin could achieve a maximal plasma concentration (Cmax) greater than the MPC of 90% of isolates (Cmax/MPC90). The overall rank of potency against S. pseudintermedius, based on Cmax/MIC, Cmax/MPC, the area under concentration–time curve (AUC)/MIC and AUC/MPC values, was in decreasing order: enrofloxacin > ciprofloxacin ≥ marbofloxacin ≥ orbifloxacin = difloxacin. Sequencing of the quinolone resistant determining region of gyrA, gyrB, grlA and grlB of resistant strains showed a base‐pair substitution in both gyrA and gyrB that resulted in Ser‐84 to Leu and Ser‐80 to Arg amino acid changes, respectively. Conclusions and clinical importance –  High doses of ciprofloxacin, enrofloxacin and marbofloxacin could minimize the selection of resistant mutants, whereas the possibility of selecting mutants with the conventional doses of difloxacin and orbifloxacin, and low clinical doses of all fluoroquinolones, seems high.