Early changes of the portal tract on microcomputed tomography images in a newly‐developed rat model for Budd–Chiari syndrome

Background and Aim: The effect of increased sinusoidal pressure on the portal tract in Budd–Chiari syndrome (BCS) is as yet not elucidated. Our aim was to investigate portal changes in a newly‐developed rat model for BCS. Methods: We created an outflow obstruction in Sprague–Dawley rats (n = 6) by diameter reduction of the inferior vena cava. Left and right liver lobes with portal vein contrast were scanned using microcomputed tomography, and volumes of the portal tree and liver parenchyma were computed by the ANALYZE software program. Results: Portal branching density was significantly lower in BCS than the shams, and decreased over time (P < 0.01). There was a significant drop in volume of both parenchyma and the portal tree in the left but not right lobes. At 6 weeks post‐surgery, the perfusion index (i.e. ratio between both volumes) became equal to (left) or even higher than (right) the shams, suggesting a new equilibrium with preserved portal perfusion. Histological findings were consistent with those observed in humans. Conclusion: As early as day 2, a significant loss of peripheral portal branches was seen, which progressed over time. Inter‐lobar differences in vascular abnormalities suggest compensatory mechanisms. Despite a decrease in both liver and portal vein volume, relative portal perfusion appeared spared.     

Sequestrum-like appearance of a multiple sclerosis brain lesion on serial magnetic resonance images.

Using serial magnetic resonance imaging, we monitored an unique lesion of the brain in a 15-year-old girl with clinically definite and laboratory-supported remitting-relapsing multiple sclerosis. During initial phases of the disease course, cystic necrosis around the plaque was observed. Later, remyelination of the central core of the lesion was speculated, as similarities in signal intensity between the core and the normal appearing white matter were partially recovered both on the T1- and the T2-weighted images.     

Peripheral vascular responses during carotid baroreceptor stimulation in normotensive and hypertensive subjects

1. The carotid baroreceptors were stimulated for 2 min by neck suction at -30 and -60 mmHg in 19 normotensive subjects and 12 patients with moderate essential hypertension. 2. Blood pressure was measured with a mercury sphygmomanometer and heart rate was derived from beat-to-beat analysis of the electrocardiogram. Blood flow was measured simultaneously at calf and finger with venous occlusion plethysmography and the vascular resistance was calculated. 3. During neck suction at -30 and -60 mmHg there was a significant decrease in arterial blood pressure and heart rate. There was a transient vasodilatation of the calf blood vessels, while there was a sustained vasoconstriction of the finger blood vessels. These results were qualitatively similar in both groups; however, there were quantitative differences. 4. These experiments show that there is a selective autonomic control of the different peripheral vascular beds by the carotid baroreceptors in both normotension and mild essential hypertension.     

Potential benefits of early aggressive immunotherapy in Susac syndrome

Susac syndrome is a rare vasculopathy of unknown aetiology, affecting prominently young women and electively targeting brain (encephalopathy), retina (visual field defects), and cochlea (hearing loss), of which optimal treatment has yet to be established. We report clinical, CSF and MRI features together with the long-term outcome in a monocentric series of eight consecutive patients with unusual sex ratio (5 male; 3 female), to define the best diagnostic/therapeutic strategy. Six patients presented with the classical clinical triad within less than 6 months after symptoms onset; two did not suffer from sensorineural hearing loss. All but one received a treatment combining high doses of methylprednisolone and cyclophosphamide intravenously. The first two patients had very delayed diagnosis (6–4 months) resulting in severe cognitive sequelae. The third one had only mildly delayed diagnosis (2 months) with subsequent behaviour impairment and severe right hypoacousia. All three were unable to return to work. The last five patients who had early diagnosis and undelayed aggressive treatment were able to resume their professional activities.     

Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine-Tuning of Their Antibiofilm Activity Spectrum and Toxicity

We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2N-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity.