Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?

The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically–modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.     

Cats and goat whey associated with Toxoplasma gondii infection in pigs

In organic livestock production systems, farm-management factors are thought to play an important role in the on-farm prevalence of Toxoplasma gondii. Serological results and the results of an HACCP analysis were combined to determine important risk factors for the prevalence of this protozoan parasite. Mathematical analysis demonstrated that feeding goat whey to pigs and the presence of a high number of cats were positively correlated to T. gondii seroprevalence in pigs. Not covering roughage and the farmers' assumption that pigs can come into contact with cat feces also showed a positive relationship. In order to decrease the risk of T. gondii infecting their pigs, farmers should limit the access and number of cats on their farms and refrain from feeding goat whey to their pigs.     

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt–Koyanagi–Harada disease

Vogt–Koyanagi–Harada (VKH) disease is an autoimmune disease leading to visual impairment. Its pathogenic mechanisms remain poorly understood. Our purpose was to investigate the distinctive protein and metabolic profiles of sweat in patients with VKH disease. In the present study, proteomics and metabolomics analysis was performed on 60 sweat samples (30 VKH patients and 30 normal controls) using liquid chromatography tandem mass spectrometry. Parallel reaction monitoring (PRM) analysis was used to validate the results of our omics analysis. In total, we were able to detect 716 proteins and 175 metabolites. Among them, 116 proteins (99 decreased and 17 increased) were observed to be significantly different in VKH patients when compared to controls. Twenty-one differentially expressed metabolites were identified in VKH patients, of which 18 included choline, L-tryptophan, betaine and L-serine were reduced, while the rest were increased. Our multi-omics strategy reveals an important role for the amino acid metabolic pathway in the pathogenesis of VKH disease. Significant differences in proteins and metabolites were identified in the sweat of VKH patients and, to some extent, an aberrant amino acid metabolism pathway may be a pathogenic factor in the pathogenesis of VKH disease.     

Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study

The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r_s=0.59; p=0.007), BA 17 (r_s=0.50; p=0.027), and BA 18 (r_s=0.48; p=0.031), and with the spatial extent of activation in BA 17 (r_s=0.059; p=0.007) and BA 18 (r_s=0.55; p=0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p=0.031) and BA 18 (p=0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.     

Toxoplasmosis,an overview with emphasis on ocular involvement

Toxoplasmosis is a common parasitic zoonosis and an important cause of abortions, mental retardation, encephalitis, blindness, and death worldwide. Although a large body of literature has emerged on the subject in the past decades, many questions about the pathogenesis and treatment of the disease remain unanswered. This review aims to provide an overview of the current insights regarding the causative parasite and the mechanisms leading to symptomatic infection with emphasis on ocular toxoplasmosis.     

Secretory IgA and lysozyme in tears of patients with Graves' ophthalmopathy

Using an enzyme linked immuno-assay (ELISA) and spectrophotometry, we determined levels of secretory IgA and lysozyme in tears of 69 patients with Graves' ophthalmopathy and 28 controls. The quantitative determination of secretory IgA and lysozyme in tears provided an impression of the functioning of the lacrimal gland in the two groups. An IgA/lysozyme ratio was calculated in both patients and controls as a parameter for the activity of the secretory IgA-producing plasma cells in the lacrimal gland. An increase in the IgA/ lysozyme ratio was observed in 23 patients (33%) and one control (3%). Half of the patients who had suffered from the disease for more than 5 years showed a raised IgA/lysozyme ratio. No correlation was found between the IgA/lysozyme ratio and the NOSPECS classification. Our findings suggest that the lacrimal gland is involved in the orbital condition produced by Graves' ophthalmopathy. In most cases the involvement occurs in patients with a long history of the disease.     

The effect of lactoferrin on complement mediated modulation of immune complex size

Earlier we showed that human lactoferrin is capable of inhibiting the complement-mediated lysis of antibody-coated erythrocytes due to an inhibition of the formation of the classical C3 convertase. In this report the effect of lactoferrin on complement mediated modulation of immune complex size was studied. Lactoferrin was shown to inhibit the complement-dependent solubilization of immune precipitates with kinetics resembling that seen by others using C2 deficient serum. Lactoferrin, however, did not affect the complement-dependent inhibition of immune precipitation. These findings confirm our earlier observations that lactoferrin has no effect on the activation of the very early complement components (C1 and C4), but inhibits C3 deposition on immune complexes which is a crucial mechanism in immune precipitate solubilization.     

Autoimmunity against corneal antigens. I. Isolation of a soluble 54 Kd corneal epithelium antigen

Corneal epithelium antibodies were detected in patients with corneal melting disease and uveitis using an immunofluorescence technique with cryostat sections of corneas obtained from various species (man, guinea pig, rabbit, mouse, rat, cow, pig). No differences in results were found using these various substrates, indicating that the autoimmune response is directed against common non-species specific corneal epithelium antigens. The serum of a patient with corneal melting disease, containing a high antibody titer against corneal epithelium was used to identify and isolate one of the bovine corneal antigens. A 54,000 dalton protein was isolated, which was shown to be the major protein present in the corneal epithelium. Absorption studies with other tissues taken from human eyes showed that cornea epithelium, cornea devoid of epithelium, ciliary body and retina contained material which cross-reacted with the isolated bovine corneal epithelium antigen, whereas iris and sclera showed no detectable cross-reaction. The incidence of autoantibodies directed against this antigen was investigated in patients with corneal melting disease, corneal transplantion and in uveitis patients using an ELISA and comparing the results with those obtained with the immunofluorescence assay on rabbit cornea sections. A positive ELISA was always associated with a positive immunofluorescence test. The presence of antibodies against the 54 Kd antigen as detected by the ELISA could be confirmed by immunoblotting in 7 out of 9 positive sera tested. A large number of sera showed a positive immunofluorescence test but a negative ELISA against the 54 Kd corneal epithelium antigen.(ABSTRACT TRUNCATED AT 250 WORDS)