Infective complications after transcatheter aortic valve implantation: results from a single centre

After its first introduction in 2002, transcatheter aortic valve implantation (TAVI) has continuously gained more foothold for the treatment of severe aortic stenosis and is nowadays a viable treatment option for inoperable patients or patients at high risk for conventional surgical aortic valve replacement. Although ideally carried out in a so-called hybrid room, incorporating both the strict hygiene and advanced life support possibilities of the operating theatre and the imaging and percutaneous arsenal of the catheterisation suite, in most centres TAVI is at present performed in the catheterisation laboratory. This may raise concern about an increased risk of infection, since there the criteria that are applied regarding disinfection and sterilisation are not as stringent as those of the operating theatre. Therefore, we retrospectively assessed the number of infective complications in patients undergoing TAVI in the catheterisation lab of our institution. Eleven out of 73 patients developed a postprocedural infection, one of which could be attributed to the procedure itself, being superinfection of a surgical groin cut-down. Our conclusion is that percutaneous aortic valve implantation in a catheterisation laboratory is not associated with an increased risk of infective complications.     

Mate choice or harassment avoidance? A question of female control at the lek

Recent studies on the reproductive behavior of fallow deer,Dama dama, propose that harassment from nonterritorial maleshas a major influence on female movements and mate selection,leading ultimately to the evolution of lek mating in this species.In order to support this statement, one must demonstrate thatfemale movements between lek and isolated territories, and amonglek males, lead to a reduction in levels of harassment. We arguethat current evidence in favor of this view is inconclusive.A quantification of the total harassment costs experienced byfemales in lek and isolated territories has never been made.In addition, female movements within the lek may actually leadto higher levels of disruption and harassment: The rate at whichfemales join male territories increases with harem size (thenumber of females present in the territory), even though haremsare disrupted increasingly with size due to a higher frequencyof intrusions by nonterritorial males. Females also join maleterritories at a higher rate while these males are engaged incopulatory sequences, but copulatory sequences are again associatedwith high levels of disruption and harem instability. In theabove studies it is argued that females are nonselective intheir mating preferences. This assessment is based on the findingthat males that adopt different reproductive strategies do notdiffer in their mating rates. Here mating rate is measured asthe number of copulations received per female-hour. There area number of reasons, however, why females exhibiting matingpreferences might remain longer with preferred males, and sothe above preference measure cannot be used to exclude the possibilitythat females are selective. More research is required to identifythe major factors influencing patterns of mate selection andthe evolution of leks in this species. We suggest a number offield tests that may help to identify these factors.     

Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease.

Niemann-Pick type C (NPC) is a neurodegenerative disorder characterized by greatly altered somatic cholesterol metabolism. The NPC1 gene has recently been cloned and shown to have sequence homology to other sterol-sensing proteins. We have used a mouse model with a disrupted npc1 gene to study the effects of the cholesterol-mobilizing compound, 2-hydroxypropyl-beta-cyclodextrins (HPBCD), on the clinical course of this disorder. Treatment with two HPBCDs, with varying levels of 2-hydroxypropyl substitution, had effects in delaying neurological symptoms and in decreasing liver cholesterol storage while a third HPBCD was without effect. The ameliorating effect was not improved by longer exposure times (commencement of exposure in utero), however, it is not known if there is transplacental transfer of HPBCDs. The combination of HPBCD with probucol or nifedipine (which have previously been shown to lower liver cholesterol in this animal model) markedly decreased liver storage of unesterified cholesterol without altering the depressed levels of esterified cholesterol. The slight effects of the HPBCDs on neurological symptoms may be partially due to their apparent non-permeation of the blood-brain barrier (BBB). This non-permeation was assayed with radioactive tracers and was also present in the mdr1a knockout mice which have greatly increased BBB permeability for many drugs. Intrathecal delivery of HPBCD by an Alzet osmotic minipump did not improve its efficacy in ameliorating neurological symptoms.     

Spectral analyses of extrinsic fluorescence of the nerve membrane labeled with aminonaphthalene derivatives

A fluorescence spectrophotometer was constructed to determine the emission spectrum of a nerve labeled with various fluorochromes. Using this spectrophotometer, the spectra of 2-p-toluidinylnaphthalene 6-sulfonate (2,6-TNS) and other aminonaphthalene derivatives in squid giant axons were determined at the peak of nerve excitation, as well as in the resting state of the axons. During nerve excitation the fluorescent light deriving from the 2,6-TNS-stained nerve undergoes a transient change in intensity. The spectrum of the light contributing to this change in intensity was found to be much narrower and sharper than the fluorescent spectrum of the light arising from labeled axons at rest. This narrow and sharp spectrum is interpreted as being derived from a transient variation in the polarity of the 2,6-TNS binding sites in the axon. In the Appendix, the results of a physicochemical investigation into the factors affecting the fluorescence of 2,6-TNS in vitro are described.     

A new “sudden fright paradigm” to explore the role of (epi)genetic modulations of the DAT gene in fear-induced avoidance behavior

Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT-KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive-like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX-HET), compared to HET rats born from WT-mother and KO-father (MAT-HET), implementing the role of maternal care on DAT modulation. We developed a “sudden fright” paradigm (based on dark-light test) to study reaction to fearful inputs in the DAT-KO, MAT-HET, MIX-HET, and WT groups. Rats could freely explore the whole 3-chambers apparatus; then, they were gently confined in one room where they experienced the fright; finally, they could freely move again. As expected, after the fearful stimulus only MAT-HET rats showed a different behavior consisting of avoidance towards the fear-associated chamber, compared to WT rats. Furthermore, ex-vivo immuno-fluorescence reveals higher prefrontal DAT levels in MAT-HET compared to MIX-HET and WT rats. Immuno-fluorescence shows also a different histone deacetylase (HDAC) enzymes concentration. Since HDAC concentration could modulate gene expression, within MAT-HET fore brain, the enhanced expression of DAT could well impair the corticostriatal-thalamic circuit, thus causing aberrant avoidance behavior (observed only in MAT-HET rats). DAT expression seems to be linked to a simply different breeding condition, which points to a reduced care by HET dams for epigenetic regulation. This could imply significant prefronto-cortical influences onto the emotional processes: hence an excessively frightful response, even to mild stressful agents, may draw developmental trajectories toward anxious and depressed-like behavior.