Mouse Anti-Human VIM Monoclonal Antibody

Background: Imipenem/relebactam is a carbapenem/beta-lactamase inhibitor combination with in vitro activity against Pseudomonas aeruginosa and Enterobacterales, including KPC producers. Objectives: To provide translational data to support the clinical utility of the imipenem/relebactam 500/250mg q6h regimen using a human-simulated regimen (HSR) of imipenem/relebactam, compared with imipenem alone, against a phenotypically and genotypically diverse population of P. aeruginosa. Methods: Twenty-nine P. aeruginosa isolates, including KPC (n = 6), PDC (n = 9), PAO (n = 4), GES (n = 5) and VIM (n = 1) producers, were used for the in vivo efficacy studies. Neutropenic mice were thigh-inoculated and randomized to receive HSRs of either imipenem 500mg q6h, imipenem 1 g q8h, imipenem/relebactam 500/250mg q6h or saline. Results: Twenty-seven of the 29 isolates examined were imipenem resistant, with 24/29 isolates showing imipenem MICs of similar to 32 mg/L. The addition of relebactam decreased the MICs up to 64-fold; imipenem/relebactam MICs ranged from 0.25 to >32 mg/L. Efficacies of the imipenem monotherapies and the imipenem/relebactam therapy were comparable for the two imipenem-susceptible organisms. Among the imipenem-resistant isolates, an increased mean growth was observed in the imipenem 500mg q6h HSR and 1 g q8h HSR treatment groups of 1.31 +/- 1.01 and 0.18 +/- 1.67 log(10) cfu/thigh, respectively. In contrast, a similar to 2 log reduction in bacterial density was observed in 27/29 (93%) of the imipenem-resistant isolates subjected to imipenem/relebactam 500/250mg q6h HSR. Conclusions: The imipenem/relebactam 500/250mg q6h HSR demonstrated superior in vivo activity compared with the conventionally employed imipenem regimens against MDR P. aeruginosa over a wide range of imipenem/relebactam MICs.

Desmin (DES) and Vimentin (VIM) exert an essential role in maintaining muscle cytoarchitecture and since are considered reliable markers for muscle regeneration, their expression has been extensively investigated in dystrophic muscles. Thus, exhibiting features similar to those of human dystrophic muscles, the present study aimed at assessing the distribution of VIM and DES proteins and the expression of the corresponding genes in Pectoralis major muscles affected by white striping (WS), wooden breast (WB), and spaghetti meat (SM) abnormalities as well as in those having macroscopically normal appearance (NORM). For this purpose, 20 Pectoralis major muscles (5/group) were collected from the same flock of fast-growing broilers to perform immunohistochemistry, immunoblotting and gene expression. Immunohistochemical analyses showed an increased number of fibers immunoreactive to both VIM and DES in WS and WB, while only a few immunoreactive fibers were observed in NORM. Concerning the protein level, if compared with NORM, a 55% increase in VIM content was found in WB affected cases (P < 0.05) thus suggesting the development of intense regenerative processes in an early-stage within these muscles. The significantly higher amount of DES (+53%) found in WS might be attributed to a progression of the regenerative processes that require its synthesis to preserve the structural organization of the developing fibers. On the other hand, significantly lower VIM and DES contents were found in SM. About gene expression, VIM mRNA levels gradually increased from the NORM to the SM group, with significantly higher gene expressions in WB and SM samples compared to the NORM group (P = 0.009 for WB vs. NORM and P = 0.004 for SM vs. NORM). Similarly, the expression of DES gene showed an increase from the NORM to WB group (P = 0.05). Overall, the findings of the present study suggest that intense regenerative processes take place in both WB and WS muscles although a different progression of regeneration might be hypothesized. On the other hand, the lack of correspondence between VIM gene expression and its protein product observed in SM suggests that VIM may also exert a role in the development of the SM phenotype.