The in vivo and in vitro toxicity of bacterial cells and their extracellular products (ECPs) from 16 strains of Photobacterium damselae subsp. damselae isolated from 7 epizootic outbreaks were evaluated. On the basis of their 50% lethal dose (LD 50 ) values (about 1 × 10 5 CFU), these strains may be considered as moderately virulent. However, their ECPs were strongly lethal for redbanded seabream Pagrus auriga causing fish death within 2 h post-inoculation (protein concentration ranged between 2.1 and 6.41 µg g -1 fish). The bacterial ECPs tested exhibited several enzymatic activities, such as amylase, lipase, phospholipase, alkaline phosphatase, esterase-lipase, acid phosphatase, and β-glucosaminidase. These ECPs displayed a strong cytotoxic effect on 4 fish and 2 mammalian cell lines, although this activity disappeared when ECPs were heated at 100°C. The virulence of the strains tested could not be related to the hemolytic activity or to the production of the toxin damselysin. Therefore, another unknown type of toxin could play an important role in the virulence mechanisms of this bacterial pathogen.KEY WORDS: Toxicity · ECP · Photobacterium damselae subsp. damselae · Cultured marine fish Resale or republication not permitted without written consent of the publisherDis Aquat Org 92: [31][32][33][34][35][36][37][38][39][40] 2010 brane, has been described (Kreger 1984, Kothary & Kreger 1985, Kreger et al. 1987. In addition, a relationship between the degree of virulence and the hemolytic activity has been demonstrated in P. damselae subsp. damselae strains isolated from fish (Fouz et al. 1993). However, Cutter & Kreger (1990) found that not all the P. damselae subsp. damselae strains presented the damselysin gene (dly), but only those strains showing intense hemolytic activity. A further study demonstrated that the presence of this gene was not correlated to the virulence in mice and fish of 17 P. damselae subsp. damselae strains isolated from different sources (Osorio et al. 2000).The extracellular products (ECPs) are produced by bacterial pathogens to facilitate the uptake of nutrients from the surrounding environment, and/or for the successful penetration and survival of pathogens inside the host (Bakopoulos et al. 2003). However, the role of ECPs in the pathogenesis of Photobacterium damselae subsp. damselae in fish is poorly known, which is a considerable disadvantage for the development of vaccines and vaccine strategies, since it has been suggested that the ECP components are major antigenic compounds of several vaccine formulations (Collado et al. 2000, Bakopoulos et al. 2004.The aim of this study was to determine the toxicity of different Photobacterium damselae subsp. damselae strains isolated from cultured diseased fish. For this purpose, we performed in vivo and in vitro assays using bacterial cultures and their ECPs. In addition, the enzymatic activities of the ECPs and their cytotoxicity in fish and mammalian cell lines were compared. MATERIALS AND METHODSBacterial strains. In this...

Plasma carnitine "insufficiency," (plasma esterified carnitine to free carnitine ratio above 0.25) was found in 21 of 48 (43.8%) patients with mitochondrial myopathy, of whom 4 also showed both total and free carnitine deficiencies in plasma. In addition, plasma levels of SCAC and LCAC were higher in patients with mitochondrial myopathy than in controls (P < 0.001 and P < 0.01, respectively). Patients diagnosed as having plasma carnitine insufficiency or deficiency were treated with L-carnitine (50-200 mg/kg per day in four daily doses). Muscle weakness improved in 19 of 20 patients, failure to thrive in 4 of 8, encephalopathy in 1 of 9, and cardiomyopathy in 8 of 8 patients. Plasma carnitine "insufficiency" provides an additional clue to the diagnosis of mitochondrial myopathy and an indication for L-carnitine therapy.

Intelligent recommendation systems can be based on 2 basic principles: collaborative filters and individual‐based agents. In this work we examine the learning function that results from these 2 general types of learning‐smart agents. There has been significant work on the predictive properties of each type, but no work has examined the patterns in their learning from feedback over repeated trials. Using simulations, we create clusters of “consumers” with heterogeneous utility functions and errorful reservation utility thresholds. The consumers go shopping with one of the designated smart agents, receive recommendations from the agents, and purchase products they like and reject ones they do not. Based on the purchase–no purchase behavior of the consumers, agents learn about the consumers and potentially improve the quality of their recommendations. We characterize learning curves by modified exponential functions with an intercept for percentage of recommendations accepted at Trial 0, an asymptotic rate of recommendation acceptance, and a rate at which learning moves from intercept to asymptote. We compare the learning of a baseline random recommendation agent, an individual‐based logistic‐regression agent, and two types of collaborative filters that rely on K‐mean clustering (popular in most commercial applications) and nearest‐neighbor algorithms. Compared to the collaborative filtering agents, the individual agent (a) learns more slowly, initially, but performs better in the long run when the environment is stable; (b) is less negatively affected by permanent changes in the consumer's utility function; and (c) is less adversely affected by error in the reservation threshold to which consumers compare a recommended product's utility. The K‐mean agent reaches a lower asymptote but approaches it faster, reflecting a surprising stickiness of target classifications after feedback from recommendations made under initial (incorrect) hypotheses.

Abnormal carnitine distribution in muscle was found in 22 of 77 patients (29%), with mitochondrial myopathy. Furthermore, total (TC) and free (FC) carnitine levels in muscle were lower in patients than in controls (P < 0.01). Muscle long-chain acylcarnitines (LCAC) were significantly increased in these patients (P < 0.01). Muscle carnitine deficiency was found in 31.5% of patients with lipid storage myopathy (LSM) and in 25.6% of patients with ragged-red fibers (RRF). Therefore, carnitine deficiency can be found in patients with mitochondrial myopathy even in the absence of LSM. Muscle levels of TC and FC were lower in patients with respiratory chain defects than in those with normal respiratory chain (P < 0.01). In contrast, LCAC levels were significantly increased (P < 0.05). Carnitine levels did not differ significantly, among patients with different respiratory-chain defects. Consequently, these patients, owing to their biochemical block, reduce progressively the muscle carnitine pool and subsequent LCAC rise, due to long-chain fatty acid (LCFA) accumulation.

In this report, we describe seven new patients with a severe deficiency of glutaryl-CoA dehydrogenase in cultured skin fibroblasts. Three of the patients studied excreted high levels of glutaric acid. The remaining four patients presented a lack of significant glutaric aciduria. However, glutaric acid was found in increased levels in CSF. In both groups of patients, the urine glutaric acid levels were not related to their metabolic condition at the time of sampling. Hypocarnitinemia was a common finding. Some patients also showed defects on respiratory chain complexes in muscle biopsy. Only one patient has a normal psychomotor development. The other six patients are severely handicapped despite the attempts of different therapies. In patients with progressive neurological deterioration with dystonia and cerebellar signs associated with temporal lobe atrophy and bilateral basal ganglia damage on MRI, a glutaric aciduria type I (GA I) should always be investigated. The presence of glutaric acid in body fluids, especially in CSF, as well as plasma carnitine levels, should be determined. These procedures can lead to the diagnosis of glutaric aciduria type I.