Neuronal Ca2+ sensor VILIP-1 leads to the upregulation of functional alpha4beta2 nicotinic acetylcholine receptors in hippocampal neurons.

The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the alpha4-subunit of the alpha4beta2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The alpha4beta2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer's disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces alpha4beta2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of alpha4beta2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the alpha4beta2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels.

Totally implantable venous power ports of the forearm and the chest: initial clinical experience with port devices approved for high-pressure injections.

OBJECTIVES: To evaluate the technical success, clinical outcome and safety of percutaneously placed totally implantable venous power ports (TIVPPs) approved for high-pressure injections, and to analyse their value for arterial phase CT scans. METHODS: Retrospectively, we identified 204 patients who underwent TIVPP implantation in the forearm (n=152) or chest (n=52) between November 2009 and May 2011. Implantation via an upper arm (forearm port, FP) or subclavian vein (chest port, CP) was performed under sonographic and fluoroscopic guidance. Complications were evaluated following the standards of the Society of Interventional Radiology. Power injections via TIVPPs were analysed, focusing on adequate functioning and catheter's tip location after injection. Feasibility of automatic bolus triggering, peak injection pressure and arterial phase aortic enhancement were evaluated and compared with 50 patients who had had power injections via classic peripheral cannulas. RESULTS: Technical success was 100%. Procedure-related complications were not observed. Catheter-related thrombosis was diagnosed in 15 of 152 FPs (9.9%, 0.02/100 catheter days) and in 1 of 52 CPs (1.9%, 0.002/100 catheter days) (p<0.05). Infectious complications were diagnosed in 9 of 152 FPs (5.9%, 0.014/100 catheter days) and in 2 of 52 CPs (3.8%, 0.003/100 catheter days) (p>0.05). Arterial bolus triggering succeeded in all attempts; the mean injection pressure was 213.8 psi. Aortic enhancement did not significantly differ between injections via cannulas and TIVPPs (p>0.05). CONCLUSIONS: TIVPPs can be implanted with high technical success rates, and are associated with low rates of complications if implanted with sonographic and fluoroscopic guidance. Power injections via TIVPPs are safe and result in satisfying arterial contrast. Conventional ports should be replaced by TIVPPs.

Sulfated hyaluronan/collagen I matrices enhance the osteogenic differentiation of human mesenchymal stromal cells in vitro even in the absence of dexamethasone.

Glycosaminoglycans (GAG) are multifunctional components of the extracellular matrix (ECM) involved in different steps of the regulation of cellular differentiation. In this study artificial extracellular matrices (aECM) consisting of collagen (Col) I and different GAG derivatives were used as a substrate for human mesenchymal stromal cells (hMSC) to study osteogenic differentiation in vitro. hMSC were cultured on aECM containing col and hyaluronan sulfates (HyaS) with increasing degrees of sulfation (DS(S)) and were compared with aECM containing col and the natural GAG hyaluronan or chondroitin 4-sulfate. hMSC were analyzed for osteogenic differentiation markers such as calcium phosphate deposition, tissue non-specific alkaline phosphatase (TNAP) and expression of runt-related transcription factor 2 (runx2), osteocalcin (ocn) and bone sialoprotein II (bspII). Compared with aECM containing Col and natural GAG all Col/HyaS-containing aECM induced an increase in calcium phosphate deposition, TNAP activity and tnap expression. These effects were also seen in the absence of dexamethasone (an established osteogenic supplement). The expression of runx2 and ocn was not altered and the expression of bspII was diminished on the col/HyaS-containing aECM. The impact of the Col/HyaS-containing aECM on hMSC differentiation was independent of the DS(S) of the HyaS derivatives, indicating the importance of the primary (C-6) hydroxyl group of N-acetylglucosamine. These results suggest that Col/HyaS-containing aECM are able to stimulate hMSC to undergo osteogenic differentiation even in the absence of dexamethasone, which makes these matrices an interesting tool for hMSC-based tissue engineering applications and biomaterial functionalizations to enhance bone formation.

[The treatment of congenital cataract in Germany--results of a survey]. / Zur Behandlung der kindlichen Katarakt in Deutschland--Ergebnisse einer Umfrage.

BACKGROUND: Among ophthalmologists congenital cataract appears to be treated very differently with regard to surgical technique and postoperative care. Most discussed items are the optimal time points for lensectomy and intraocular lens implantation, the surgical approach (via anterior chamber or pars plana), details of secondary cataract prophylaxis and the refractive adjustment. MATERIALS AND METHODS: We conducted a written survey of 113 eye hospitals or private ophthalmic surgeons in Germany on details of the congenital cataract treatment in 2005. RESULTS: We received feedback from 60 institutions (53 % response rate). The favoured approach for lensectomy was the anterior chamber (75 %). 95 % of institutions leave the capsular ring intact. The refraction of the postoperative contact lens was mainly chosen to be myopic (76 %). Intraocular lens implantation was performed mostly from an age of two years onwards (50 %) or between three and six years (37 %). Only one institution implanted from the sixth month of life. In order to compensate for the myopic shift 62 % chose a hyperopic lens refraction at implantation. CONCLUSIONS: The treatment of congenital cataracts in Germany is performed rather heterogeneously. More clinical studies are required to answer the open questions.

[Haptoglobin type and isoantibodies (anti-A and anti-B)]. / Haptoglobintyp und Isoantikörper (Anti-A und Anti-B).

In 582 sera of blood donors of the groups A1, A2, B and 0 the Hp type as well as the anti-A or anti-B isoantibody titres respectively were determined. The frequency distribution of isoantibody titres in serum samples with different Hp-type were compared. As far as the numerical difference of distribution was concerned there was only one significant observation in the group of B alpha--titres of test persons with a different Hp-type. On the basis of these findings the following Hp-type/isoantibody relation can be established: low anti-A or anti-B titres respectively (approximately 1:8) will occur more frequently in persons with the Hp-type 1-1, higher titres (approximately 1:64) are to be found predominantly in persons with Hp2 genes. These findings are in accordance with other results, on the basis of which is was suggested that persons with Hp2 gene product have a higher immunogenic reactivity in comparison to type Hp 1-1.

[Effect of human uremic serum on the survival of fetal rat hepatocytes]. / Einfluss von humanem urämischem Serum auf die Vitalität fetaler Rattenhepatozyten.

Children suffering from chronic renal insufficiency frequently show a liver cell damage. It is not clarified, whether this damage is caused immediately by chronic renal insufficiency. In the model of fetal rat hepatocytes, which were isolated by trypsin digestion, we have investigated the influence of normal and uremic serum on the lactate dehydrogenase release and the staining with trypan blue, respectively. Fetal rat hepatocytes under incubation conditions seems to be a useful model in the investigation of the influence of uremic metabolism on the liver cell. In our liver cell model the uremic serum did not influence the membrane permeability of hepatocytes for macromolecules. However, the viability of hepatocytes was impaired by 23% compared with normal serum. The vitality-reducing factor of the uremic serum is not dialysable.

[Effect of uremic plasma fractions of different molecular sizes on the filterability of red blood cells]. / Der Einfluss urämischer Plasmafraktionen unteschiedlicher Molekülgrösse auf die Filtrabilität roter Blutzellen (rBZ).

Behaviour of the filtration of red blood cells (rbc) passed through a filter paper was investigated. The rbc were incubated in fractions of blood plasma with different molecular mass (MM). By means of an Amicon membrane XM-50 the separation of plasma from healthy and uremic patients (children) was performed into two parts of different molecular sizes one of these was the concentrate (MM more than 50 000 = K) and the other was the ultrafiltrate (MM below 50 000 = UF). By a second step the UF was divided (Amicon membrane UM-50 into an UF1 (MM below 500) and into an UF2 (MM 500 to 50 000). In addition a hemofiltrate (MM below 5 000) was used for the incubation too. This hemofiltrate was made form pooled plasma of healthy and uremic patients, respectively. Rbc was incubated in both different fractions of plasma and hemofiltrate at a temperature of 37 degrees C and for a duration of 60 min. The pH-level and the osmolality were physiological. Under the influence of uremic UF the flexibility of rbc was clearly decreased. The UF1 had the most effect of the decrease of flexibility. Therefore the small substances which are easy dialysable play also an important role in the damage of rbc in the uremia.

[Pregnancy after malignant melanoma. A follow-up of 23 patients]. / Schwangerschaft nach malignem Melanom. Verlaufsbeobachtung bei 23 Patientinnen.

There is little known on the risks associated with pregnancy occurring after primary therapy of a malignant melanoma. Out of a total of 2850 melanoma patients there were 23 women (20 in stage I, 3 in stage II) in whom 33 pregnancies occurred in the course of the follow-up. No metastases developed in 18 patients with a total of 25 pregnancies whereas a relapse occurred in 3 patients in stage I and 2 patients in stage II. The induction of metastases by the pregnancy in 3 of these patients is unlikely owing to the absence of a temporal relationship or because of an existing stage II and only in 2 patients did the temporal relationship between spreading of the tumor and pregnancy suggest an influence of pregnancy on malignant melanoma.