The impact of dendrimer-grafted modifications to model silicon surfaces on protein adsorption and bacterial adhesion

In the oral cavity, omnipresent salivary protein films (pellicle) mediate bacterial adhesion and biofilm formation on natural tissues as well as on artificial implant surfaces, which may cause serious infectious diseases like periimplantitis. The purpose of this in?vitro study was to investigate the adsorption/desorption behaviour of human saliva on model surfaces grafted with polyamidoamine (PAMAM) dendrimer molecules compared to self-assembled monolayers (SAMs) exhibiting the same terminal functions (-NH(2), -COOH) by two complementary analytical methods. Furthermore, the role of saliva conditioning of PAMAM and analogous SAM modifications on the adhesion of Streptococcus gordonii DL1, an early oral colonizer, was investigated. In contrast to SAMs, PAMAM-grafted surfaces showed reduced streptococcal adherence in the absence of pre-adsorbed saliva similar to the level obtained for poly(ethylene glycol) (PEG) coatings. Moreover, coatings of PAMAM-NH(2) maintained their bacteria-repellent behaviour even after saliva-conditioning. As a general outcome, it was found that lower amounts of protein adsorbed on PAMAM coatings than on analogous SAMs. Since this study demonstrates that covalently bound PAMAM dendrimers can modulate the oral bacterial response, this approach has significant potential for the development of anti-adhesive biomaterial surfaces that are conditioned with proteinaceous films.     

Successful allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia during respiratory failure and invasive mechanical ventilation

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for various hematologic disorders. However, life-threatening adverse events resulting from treatment-related toxicity, severe infections, and/or graft-versus-host disease (GvHD) can occur. We report on a 64-year-old patient suffering from secondary acute myeloid leukemia (AML) who underwent successful allogeneic HSCT while on invasive mandatory ventilation (IMV). The patient received reduced intensity conditioning (RIC) according to the FLAMSA-protocol. Acute respiratory failure occurred one day before scheduled HSCT. Following emergency endotracheal intubation the patient was transferred to the intensive care unit (ICU). Because of respiratory deterioration, stem cell infusion was postponed. After stabilization of respiratory parameters, HSCT was performed during IMV which was continued for seven days. Following hematopoietic regeneration the patient was discharged in good condition on day 35 after HSCT. This case illustrates that intubation and mechanical ventilation do not necessarily exclude leukemic patients from HSCT.     

Science in time of crisis

A crisis usually poses novel challenges that cannot be met with existing knowledge. To confront the unexpected, we need scientific inquisitiveness and long-term basic research. Narrowly focused research programs cater to short-term thinking and are rarely an effective way to spend precious public funds.     

Atypical neuroleptic risperidone modulates glial functions in C6 astroglial cells

Risperidone has demonstrated therapeutic advantages over conventional neuroleptics and offers a valuable emerging option for the treatment of social behavior associated with autistic disorder. Considering the putative involvement of astroglial cells in neuropsychiatric disorders, we investigated the effect of risperidone on parameters of astrocyte activity — glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) levels. Risperidone was able to induce a significantly increase on glutamate uptake (32%); GS activity (15%); GSH levels (58%). These findings imply the perspectives for further investigations directed on astrocytes from different brain areas. Our present results suggest that risperidone might exert its neuroprotective effects against brain illness at least partially via modulation of astrocyte functions.     

Gap junction inhibitors modulate S100B secretion in astrocyte cultures and acute hippocampal slices

Astrocytes sense, integrate, and respond to stimuli generated by neurons or neural injury; this response involves gap junction (GJ) communication. Neuronal vulnerability to injury increased when cocultures of astrocytes and neurons were exposed to GJ inhibitors. However, GJ uncoupling could limit the extension of a lesion. We investigated a possible link between GJ communication and S100B secretion. S100B is a calcium‐binding protein of 21 kDa that is predominantly expressed and secreted by astrocytes, which has trophic paracrine activity on neurite growth, glial proliferation, and neuronal survival. GJ inhibitors were analyzed in isolated astrocytes in primary cultures from hippocampus, acute hippocampal slices, and C6 glioma cells, which were used as a negative control. Our data indicate that GJ blocking stimulates S100B secretion in astrocyte cultures and acute hippocampal slices. Different assays were used to confirm cell integrity during exposure to GJ inhibitors. S100B secretion was observed with different types of GJ inhibitors; the resulting event was dependent on time, the nature of the inhibitor, its putative molecular target of GJ blocking, and/or the cell preparation used. Only carbenoxolone induced a fast and persistent increase in S100B secretion in both preparations. Endothelin‐1 increased S100B secretion in astrocyte cultures at 1 hr, but a decrease was observed at 6 hr or in acute hippocampal slices. Physiologically, a local GJ closure associated with release of S100B in injury conditions favors the idea of a common mechanism available to limit the extension of lesion and increase the chances of cell survival. © 2009 Wiley‐Liss, Inc.