Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV)

Abstract: The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.     

Reversibility of experimental acute renal failure in rats: assessment with USPIO-enhanced MR imaging

The purpose of this study was to evaluate the potential reversibility of kidney lesions in an experimental model of acute renal failure using ultra-small particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. This study was conducted in 21 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Thirteen rats received selective intraarterial renal administration of diatrizoate (370 mg/ml) and were compared with two control groups, including six animals injected with saline and two noninjected animals. MR imaging was performed 28 hours, 8 days, and 22 days after the procedure. Each MR session included axial and coronal T1- and coronal T2-weighted images before and after intravenous administration of 60 micromol Fe/kg of USPIO. The rats were sacrificed immediately after the last MR session for pathologic evaluation. MR images were qualitatively and quantitatively interpreted with respect to pathologic data, and differences were statistically studied. At day 22, histology showed 4 severely diseased kidneys with focal areas of necrosis, 5 mildly diseased kidneys with tubular vacuolization, and 12 normal kidneys. On quantitative data, a high correlation between the percentage of negative enhancement and histologic data was observed (P < 0.05). Qualitative interpretation showed a sensitivity and specificity of USPIO-enhanced T2-weighted MR images of 88% and 91%, respectively. Follow-up enhancement curves showed a constant increase of intrarenal USPIO negative enhancement in normal kidneys between day 1 and day 22, whereas all severely involved kidneys displayed higher USPIO negative enhancement at day 1 without significant changes over time until day 22. USPIO may be useful for in vivo follow-up of the reversibility of experimentally induced iodinated contrast media renal impairment in animals.     

The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update

Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.     

Results of using botulism toxin in the treatment of spasmodic dysphonia

Spasmodic Dysphonia (SD) is a dystonia involving laryngeal musculature thus causing a characteristic voice disorder. Two main types of SD have been described. The adductor type is the commonest and it is characterized by a strain-strangle, choked voice. The abductor type can be distinguished from the previous one by episodes of a blown and whispering voice, interrupting speech. Botulism toxin (BTX) has demonstrated to be the most effective treatment for this condition. Thirty patients diagnosed of SD (twenty-nine adductor type/one abductor type) were included. Their degree of dysphonia was evaluated using both functional and visual-analogue scales. They were treated with BTX vocal cord injections using a percutaneous technique under EMG guidance. Improvements up to a 100% of the normal vocal function were obtained, with an average of 82% in the adductor type. The adverse effects were mild and transient. Hypophonia affected 61.3% of patients lasting an average of 11.3 days. Dysphagia was reported in 44.1% of cases lasting an average of 5.8 days.     

The usefulness of two-dimensional echocardiography in the diagnosis of an interventricular aneurysm]

The ventricular septal defect (VSD) may close spontaneously in the first few years of life. The closure occurs by muscle's growth of the borders of the defect or by the appearance of an aneurysm of ventricular septum composed mostly by tricuspid tissue. We believe that the two-dimensional echocardiography is the best method to determine the mechanisms that take part in the aneurysm formation. The study was carried out on 58 patients with aneurysms of ventricular septum observed in 230 patients with ventricular septal defects. 29 were male and 29 were female patients. The mean age at the time of diagnosis of aneurysm was 30 months (range 1 month-13 years). Forty seven patients had a perimembranous ventricular septal defect (perimembranous inlet 29, perimembranous trabecular nine, perimembranous outlet nine and of mixed's type seven), muscular defect nine (muscular inlet seven, and muscular trabecular two) and VSD closed in two. The size of the defect was 0.47 +/- 0.2 cm (range 0.2-1.1). In 16 the defect was larger than 0.6 cm. Thirty two patients had associated anomalies. On study the aneurysm in relation with tricuspid valve leaflets: in 27 cases (46.3%), the aneurysm was entirely formed by tricuspid septal leaflets tissue (17 had perimembranous ventricular septal defect and seven muscular), in eight (13.6) the aneurysm had tricuspid valve leaflets and interventricular component of the membranous septum tissue (five perimembranous defect and two muscular) and in another 16 cases membranous septum tissue only. In 7 patients the origin of the aneurysm wasn't confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylaxis of iodinated contrast media-induced nephropathy: a pharmacological point of view

Iodinated contrast media are a frequent cause of acute renal failure, especially in patients whose renal function is already impaired. In addition to hydration, which remains the most commonly acknowledged means of protection, numerous pharmacological approaches for the prophylaxis of contrast nephropathy have been tested so far. They include diuretics, calcium channel blockers, adenosine receptor antagonists, N-acetylcysteine, low-dose dopamine and the dopamine D1 receptor agonist fenoldopam, endothelin receptor antagonists, and even captopril. The present review of the literature critically discusses the drugs used to prevent contrast nephropathy from a pharmacological point of view.     

Characterization of monkey enteropathogenic Escherichia coli (EPEC) and human typical and atypical EPEC serotype isolates from neotropical nonhuman primates

Enteropathogenic Escherichia coli (EPEC) has been associated with infantile diarrhea and mortality in humans in developing countries. While diarrhea is also a major problem among primates kept in captivity, the role of E. coli is unclear. This study was designed to characterize diarrheagenic E. coli recovered from the feces of 56 New World nonhuman primates, primarily marmosets (Callithrix spp.). Seventeen of the 56 primates had signs of diarrhea and/or enteritis. E. coli recovered from feces from these animals was tested by PCR for genes encoding virulence factors of diarrheagenic E. coli and for patterns of adherence to HeLa cells. In addition, isolates were characterized by the fluorescence actin staining test and by their ability to induce attaching and effacing lesions. PCR for the eae gene was positive in 10 of the 39 (27%) apparently healthy animals and in 8 of the 17 (47%) animals with diarrhea and/or enteritis. Colonies of eae(+) E. coli were serotyped and examined by PCR for genes encoding EPEC virulence markers. The eae(+) E. coli isolates recovered from both healthy and sick nonhuman primates demonstrated virulence-associated attributes similar to those of EPEC strains implicated in human disease and are designated monkey EPEC. The results presented here indicate that EPEC may be a significant pathogen for nonhuman primates, deserving further investigation. The similarities between the affected animals investigated in this study and human EPEC infections suggest that marmosets may represent an important model for EPEC in humans.