Tabletten aus Papier – tablets made from paper – zur oralen Applikation schwerlöslicher Wirkstoffe

Im Rahmen der vorliegenden Arbeit wurden Tabletten aus Papier als orale Darreichungsform für smartFilms aus herkömmlichen Papiersorten erstmalig hergestellt und charakterisiert. Unter der Zielsetzung die optimal geeignete Papiergrundlage für die Produktion der Tabletten zu ermitteln, wurden diese systematisch auf ihre pharmazeutische Qualität gemäß des Pharm. Eur. und auf ihre Eignung Wirkstoffe amorph zu stabilisieren untersucht. Um eine großtechnische Produktion von Tabletten aus Papier zu gewährleisten, wurden Pellets und Pulver aus Papier hergestellt und auf ihre Eignung einen schwerlöslichen Wirkstoff amorph zu stabilisieren innerhalb einer proof of concept Studie untersucht

Evidence of re-osseointegration after electrolytic cleaning and regenerative therapy of peri-implantitis in humans: a case report with four implants.

OBJECTIVE To evaluate re-osseointegration after electrolytic cleaning and regenerative therapy of dental implants with peri-implantitis in humans. MATERIAL AND METHODS Four dental implants that developed peri-implantitis underwent electrolytic cleaning followed by regenerative therapy with guided bone regeneration. All four implants developed recurrent peri-implantitis and were therefore explanted 6 to 13 months later. Radiographic bone level, probing depth, and bleeding on probing were determined at the time of surgery, 6 months later, and before implant retrieval. The peri-implant tissues were histologically and histomorphometrically analyzed. RESULTS All four implants demonstrated radiographic and histological bone gain, reduced probing depth, and bleeding on probing. Radiographic bone gain was 5.8 mm mesially and 4.8 mm distally for implant #1, 3.3 mm and 2.3 mm for implant #2, 3.1 mm and 0.5 mm for implant #3, and 3.5 mm and 2.8 mm for implant #4. The histometric mean and maximum vertical bone gain for implant #1 to #4 was 1.65 mm and 2.54 mm, 3.04 mm and 3.47 mm, 0.43 mm and 1.27 mm, and 4.16 mm and 5.22 mm, respectively. The percentage of re-osseointegration for implant #1 to #4 was 21.0%, 36.9%, 5.7%, and 39.0%, respectively. In one implant, the newly formed bone was deposited directly onto calculus on the implant surface. CONCLUSIONS We found that (1) re-osseointegration is possible on a formerly contaminated implant surface and (2) the electrolytic cleaning process seems to be effective enough at sites with calculus residues. CLINICAL RELEVANCE Since re-osseointegration can be achieved by electrolytic cleaning, this decontamination technique may be considered as a future treatment concept

Branch point strength controls species-specific CAMK2B alternative splicing and regulates LTP

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific CAMK2B alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing novel mechanistic insight into cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9, we introduce a weaker, human branch point sequence into the mouse genome, resulting in strongly altered Camk2b splicing in the brains of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point–controlled CAMK2B alternative splicing with a fundamental function in learning and memory

vPIF-1 is an insulin-like antiferroptotic viral peptide

Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin receptors (IRs) and insulin-like growth factor receptors. The homology of VILPs includes highly conserved disulfide bridges. However, the binding affinities to IRs were reported to be 200- to 500-fold less effective compared to the endogenous ligands. We therefore speculated that these peptides also have noninsulin functions. Here, we report that the LCDV-1 VILP can function as a potent and highly specific inhibitor of ferroptosis. Induction of cell death by the ferroptosis inducers erastin, RSL3, FIN56, and FINO2 and nonferroptotic necrosis produced by the thioredoxin-reductase inhibitor ferroptocide were potently prevented by LCDV-1, while human insulin had no effect. Fas-induced apoptosis, necroptosis, mitotane-induced cell death and growth hormone-releasing hormone antagonist-induced necrosis were unaffected, suggesting the specificity to ferroptosis inhibition by the LCDV-1 VILP. Mechanistically, we identified the viral C-peptide to be required for inhibition of lipid peroxidation and ferroptosis inhibition, while the human C-peptide exhibited no antiferroptotic properties. In addition, the deletion of the viral C-peptide abolishes radical trapping activity in cell-free systems. We conclude that iridoviridae, through the expression of insulin-like viral peptides, are capable of preventing ferroptosis. In analogy to the viral mitochondrial inhibitor of apoptosis and the viral inhibitor of RIP activation (vIRA) that prevents necroptosis, we rename the LCDV-1 VILP a viral peptide inhibitor of ferroptosis-1. Finally, our findings indicate that ferroptosis may function as a viral defense mechanism in lower organisms

Evolution of pathogenicity and sexual reproduction in eight Candida genomes

Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.publishe