Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control

Background  Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and angiogenesis. It has been reported that vascular endothelial growth factor (VEGF) is overexpressed in lesional psoriatic skin and its serum levels are significantly elevated in patients with moderate to severe disease.
Objective  This study aims to evaluate the possible role of VEGF in the pathogenesis of psoriasis, and its significance as an indicator of disease severity and control.
Methods  Thirty patients with moderate to severe psoriasis and 10 healthy controls were subjected to baseline evaluation of VEGF. Patients were divided into three groups according to the received treatment: psoralen plus ultraviolet A (PUVA) thrice weekly (group 1), acitretin 50 mg daily (group 2), and combined PUVA twice weekly and acitretin 25 mg daily (group 3).Treatment continued for 16 weeks or up to clinical cure. Every patient was subjected to severity evaluation by Psoriasis Area and Severity Index (PASI) and measurement of serum VEGF before and after treatment.
Results  Mean serum levels of VEGF were significantly elevated in patients (327 ± 66.2 pg/mL) than control subjects (178 ± 83.4 pg/mL). A highly significant correlation was found between VEGF and PASI score, but not with other variables. The best clinical response, the least side-effects and the highest reduction of VEGF serum levels were achieved by the combined therapy.
Conclusion  The present study supported the proposed role of VEGF in the pathogenesis of psoriasis, and suggested that it could serve as a good indicator of disease severity and control.     

Presence and characterization of extraintestinal pathogenic Escherichia coli virulence genes in F165-positive E. coli strains isolated from diseased calves and pigs

The virulence genotype profile and presence of a pathogenicity island(s) (PAI) were studied in 18 strains of F165-positive Escherichia coli originally isolated from diseased calves or piglets. On the basis of their adhesion phenotypes and genotypes, these extraintestinal pathogenic strains were classified into three groups. The F165 fimbrial complex consists of at least two serologically and genetically distinct fimbriae: F165(1) and F165(2). F165(1) is encoded by the foo operon (pap-like), and F165(2) is encoded by fot (sfa related). Strains in group 1 were foo and fot positive, strains in group 2 were foo and afa positive, and strains in group 3 were foo positive only. The strains were tested for the presence of virulence genes found mainly in extraintestinal pathogenic E. coli (ExPEC) strains. Although all the strains were positive for the papA variant encoding F11 fimbriae incD, traT, and papC, the prevalence of virulence genes commonly found in PAIs associated with ExPEC strains was highly variable, with strains of group 2 harboring most of the virulence genes tested. papG allele III was detected in all strains in group 1 and in one strain in group 3. All other strains were negative for the known alleles encoding PapG adhesins. The association of virulence genes with tRNA genes was characterized in these strains by using pulsed-field gel electrophoresis and DNA hybridization. The insertion site of the foo operon was found at the pheU tRNA locus in 16 of the 18 strains and at the selC tRNA locus in the other 2 strains. Furthermore, 8 of the 18 strains harbored a high-pathogenicity island which was inserted in either the asnT or the asnV/U tRNA locus. These results suggest the presence of one or more PAIs in septicemic strains from animals and the association of the foo operon with at least one of these islands. F165-positive strains share certain virulence traits with ExPEC, and most of them are pathogenic in piglets, as tested in experimental infections.     

Identification of an inducible bacteriophage in a virulent strain of Streptococcus suis serotype 2

Streptococcus suis infection is considered to be a major problem in the swine industry worldwide. Most virulent Canadian isolates of S. suis serotype 2 do not produce the known virulence markers for this pathogen. PCR-based subtraction hybridization was adapted to isolate unique DNA sequences which were specific to virulent strains of S. suis isolated in Canada. Analysis of some subtracted DNA clones revealed significant homology with bacteriophages of gram-positive bacteria. An inducible phage (named Ss1) was observed in S. suis following the incubation of the virulent strain 89-999 with mitomycin C. Phage Ss1 has a long noncontractile tail and a small isometric nucleocapsid and is a member of the Siphoviridae family. Ss1 phage DNA appears to be present in most Canadian S. suis strains tested in this study, which were isolated from diseased pigs or had proven virulence in mouse or pig models. To our knowledge, this is the first report of the isolation of a phage in S. suis.     

Effects of the superoxide dismutase-mimic compound TEMPOL on oxidant stress-mediated endothelial dysfunction

The aim of this study was to investigate the effects of oxidant stress on endothelium-dependent and endothelium-independent arterial relaxation. For this, oxidant stress was generated by preincubation of rat aortic rings (RARs) in either 25 mM glucose (mimicking hyperglycemic stress) or 0.5 mM pyrogallol (a superoxide generator) and the effects of the superoxide dismutase (SOD)-mimetic compound 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy free radical (TEMPOL) on the vasorelaxant and cGMP-producing effects of acetylcholine (ACh) and glyceryl trinitrate (GTN) in control RARs and RARs exposed to oxidant stress were examined. Pyrogallol, and to a lesser extent high glucose concentration, enhanced the contractile response of RARs to phenylephrine and markedly inhibited the vasorelaxant response to ACh. Although they existed, the inhibitory effects of high glucose and pyrogallol on the vasorelaxant response to GTN were less profound, especially with pyrogallol. Moreover, both pyrogallol and high glucose concentration inhibited the basal and the ACh-induced vascular cyclic guanosine monophosphate (cGMP) production. Treatment with TEMPOL (1-5 mM) slightly increased the ACh and GTN-induced cGMP levels in control RARs but had a significant effect in high glucose and pyrogallol-pretreated RARs. Additionally, concomitant treatment of RARs with TEMPOL (5 mM) abolished the difference in the relaxation response between control RARs and RARs exposed to either pyrogallol or high glucose concentration. These results further support the theory that reactive oxygen species (ROS), especially superoxide, play a key role in mediation of endothelial dysfunction accompanying diabetes, probably through their effects on the ability of the endothelium to synthesize, release or respond to endogenous nitric oxide (NO) or NO donated by nitrovasodilators.     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.