Disruption of the blood-brain barrier by intra-arterial administration of papaverine: a technical note

INTRODUCTION: Various endovascular techniques can be used to treat cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH) including intra-arterial administration of vasodilator drugs such as papaverine or nicardipine and balloon dilatation of the affected vessel segment. Papaverine is known to have side effects, and we report a possible new one. MATERIALS AND METHODS: After the treatment of cerebral vasospasm in a SAH patient by intra-arterial administration of papaverine into the left posterior cerebral artery, severe mesencephalic extravasation of blood and contrast media was detected. RESULTS: After reviewing the literature, the authors conclude that interruption of the blood-brain barrier by papaverine most likely combined with a secondary hyperperfusion phenomena, and perhaps a direct toxic effect on brain tissue was the mechanism of this major complication. CONCLUSION: In treating vasospasm in areas with a high density of perforating arteries, especially in the posterior circulation, papaverine should be used cautiously because a safe regimen has yet to be established. In this situation, alternative agents such as calcium channel blockers could be considered, but evidence-based data are still missing

Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage

Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa

Deviations in Circulating TNF α

Objectives. Tumor necrosis factor alpha (TNFα) plays a pivotal role in the inflammatory host response. The serum-level of TNFα and the production of TNFα by lympho/monocytes, however, seem to show high individual variations. The goal of the present study was to investigate the variations and inducibility of TNFα-activity in two age-groups of healthy volunteers. Methods. Sixty elderly, healthy volunteers were studied. These persons were free of malignant diseases, and within three months, they did not have any trauma or inflammatory disease and were not taking any steroids or nonsteroid anti-inflammatory drugs. Thirty young volunteers were also included. Blood samples were taken; lympho/monocytes were separated and cultured with or without endotoxin (LPS) stimulation. Serum and culture supernatant TNFα levels were determined by bioassay using WEHI 164 cells. Results. The results indicated significant individual variations in TNFα levels of healthy volunteers irrespective of age. Subgroups with low, middle, and high serum TNF-levels were distinguished. In about 50% of volunteers with low serum-TNFα activity, LPS stimulation failed to increase the TNFα production by isolated lympho/monocytes. Conclusion. Our data suggest a chance to select individuals with enhanced sensitivity for septic complications

Synthetic Heparan Sulfate Oligosaccharides Inhibit Endothelial Cell Functions Essential for Angiogenesis

Heparan sulfate (HS) is an important regulator of the assembly and activity of various angiogenic signalling complexes. However, the significance of precisely defined HS structures in regulating cytokine-dependent angiogenic cellular functions and signalling through receptors regulating angiogenic responses remains unclear. Understanding such structure-activity relationships is important for the rational design of HS fragments that inhibit HS-dependent angiogenic signalling complexes.We synthesized a series of HS oligosaccharides ranging from 7 to 12 saccharide residues that contained a repeating disaccharide unit consisting of iduronate 2-O-sulfate linked to glucosamine with or without N-sulfate. The ability of oligosaccharides to compete with HS for FGF2 and VEGF165 binding significantly increased with oligosaccharide length and sulfation. Correspondingly, the inhibitory potential of oligosaccharides against FGF2- and VEGF165-induced endothelial cell responses was greater in longer oligosaccharide species that were comprised of disaccharides bearing both 2-O- and N-sulfation (2SNS). FGF2- and VEGF165-induced endothelial cell migration were inhibited by longer 2SNS oligosaccharide species with 2SNS dodecasaccharide activity being comparable to that of receptor tyrosine kinase inhibitors targeting FGFR or VEGFR-2. Moreover, the 2SNS dodecasaccharide ablated FGF2- or VEGF165-induced phosphorylation of FAK and assembly of F-actin in peripheral lamellipodia-like structures. In contrast, FGF2-induced endothelial cell proliferation was only moderately inhibited by longer 2SNS oligosaccharides. Inhibition of FGF2- and VEGF165-dependent endothelial tube formation strongly correlated with oligosaccharide length and sulfation with 10-mer and 12-mer 2SNS oligosaccharides being the most potent species. FGF2- and VEGF165-induced activation of MAPK pathway was inhibited by biologically active oligosaccharides correlating with the specific phosphorylation events in FRS2 and VEGFR-2, respectively.These results demonstrate structure-function relationships for synthetic HS saccharides that suppress endothelial cell migration, tube formation and signalling induced by key angiogenic cytokines

A new method for evaluating host preference of Cuscuta species

A new method is presented for evaluating the host preference of dodders. This technique takes account of the frequency and intensity of infestations, the proportion of the resource use and availability, the resource distribution as well as the defence mechanisms of the hosts. The process categorises not only the host species but each infestation, respectively, and establishes an order of preference among the host species. This method considers also the fact that the preference status of a host species may considerably vary under different circumstances (under different species environments and/or in different habitats). The method was tested on Cuscuta europaea at 75 localities in Hungary. During the study 1,189 plant-parasite relationships were examined and categorised. This dodder was found to parasitise almost every plant, which came into contact with it in the natural habitats, however, the intensity of infestations greatly varied among the host species. A list of the most preferred, most avoided and the most frequently parasitised accessory host species was prepared for C. europaea. The results revealed that plant species of the nitrogen-poor habitats and species from Poaceae could not be preferred hosts for this dodder