The in vitro activities of DA-7157, a novel oxazolidinone, against clinical isolates of Nocardia brasiliensis and Mycobacterium tuberculosis were determined. Equal MIC 50 s and MIC 90 s (0.25 and 0.5 g/ml, respectively) were found for susceptible and multidrug-resistant isolates of M. tuberculosis. The N. brasiliensis isolates showed an MIC 90 of 1 g/ml and an MIC 50 of 1 g/ml. The DA-7157 prodrug, DA-7218, exhibited similar MICs for M. tuberculosis but fivefold-higher MICs for N. brasiliensis.Oxazolidinones are a new, unique class of synthetic antibacterial agents effective against many gram-positive bacteria, including aerobic pathogenic actinomycetes of the genera Mycobacterium, Nocardia, and Actinomadura (3,7,8,9). Linezolid, the first oxazolidinone on the market, has been proven to be active in animal models (2), as well as in clinical trials with patients infected with Nocardia spp. (5) or Mycobacterium tuberculosis (1). Oxazolidinones selectively inhibit bacterial protein synthesis by binding to bacterial 23S rRNA of the 50S subunit and preventing the formation of a functional 70S initiation complex (6). The antibacterial activity of oxazolidinones depends on the affinity for the site of action on the ribosome; therefore, by modifying their chemical structure, new compounds with improved antimicrobial activity can be obtained.Recently, a new oxazolidinone, DA-7157, was shown to be active in vitro against several gram-positive species, with the observation of a level of activity superior to that of linezolid (K. Lee, J. H. Yum, D. Yong, Y. Chong, S. H. Choi, and J. K. Rhee, Abstr. 45th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-1419Chemother., abstr. F- , 2005. The DA-7157 compound is produced by the metabolism of a highly hydrophilic prodrug, DA-7218 (Fig. 1) . The stock solution of DA-7218 was prepared in distilled water. In order to compare our results, we also performed susceptibility assays with linezolid, a drug previously tested in vitro against M. tuberculosis with good results. The latter was obtained from Pharmacia and Upjohn (Kalamazoo, Mich.), and the stock was prepared in 7H9GC broth. All working solutions were diluted in 7H9GC broth to a 2ϫ concentration prior to their addition to the microplates. Dimethyl sulfoxide controls were also run to determine its possible toxicity on the microorganisms.A total of 95 M. tuberculosis isolates were tested, including 8 isolates resistant to isoniazid, 1 isolate resistant to rifampin, and 25 clinical isolates resistant to both isoniazid and rifampin. The susceptibility assays were performed by the proportion method. For controls, we ran M. tuberculosis H37Rv and H37Ra. In order to determine the susceptibilities to linezolid, DA-7157, and DA-7218, the broth microdilution method with Alamar Blue was utilized (8). In brief, mycobacterial suspensions were prepared in 0.04% (vol/vol) Tween 80-0.2% bovine serum albumin so their turbidities equaled a McFarland turbidity standard of 1. Suspensions were further diluted 1:25 in 7H9GC broth. The rest of...
The hypo-osmotic test has been used successfully on equine semen and was considered to be a simple and accessible method which could be a useful addition to routine equine semen analysis. It was therefore of interest to determine whether the hypo-osmotic test is significantly correlated to proposed criteria of fertility. The stallions were divided into two groups on the basis of threshold levels of fertility. A significant difference (P<0.05) was found between the two groups for the following parameters: progressive motility, morphologically normal spermatozoa, percentage of swelling with the hypo-osmotic test, percentage of pregnant mares and number of services per pregnancy. The hypo-osmotic test provided a simple evaluation of membrane function and the results obtained show stallions with low swelling scores (<40%) to be of doubtful fertility. The hypo-osmotic test was not correlated with percentage of pregnant mares but showed a tendency to correlate with the number of services per pregnancy, therefore it could be an additional method for evaluating stallion fertility. Further studies are needed to confirm this observation.
The in vitro sensitivities of 30 strains of Nocardia brasiliensis to DA-7867, gatifloxacin, moxifloxacin, and BMS-284756 (garenoxacin) were determined using the broth microdilution method. All N. brasiliensis strains were sensitive to these antimicrobials. The most active drug in vitro was DA-7867, with a MIC at which 90% of the isolates tested were inhibited of 0.03 g/ml and a MIC at which 50% of the isolates tested were inhibited of 0.06 g/ml.
SYNOPSIS Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 450 when compared with those of healthy control subjects.Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 700 respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested.
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