Dendrimer and an active substance occluded in the dendrimer : a process for the preparation thereof and a process for releasing the active substance

The invention relates to a dendrimer composition in which an effective number of the terminal functionalities are provided with blocking agents, and at least one active substance species is occluded in the dendrimer. A blocking agent is a sufficiently sterically sized compound which readily enters into a chemical bond with a terminal group of a dendrimer but which can also be split off from the dendrimer or can be modified without affecting the chemical structure of the dendrimer and the occluded active substance. The blocking agent can also be provided with a protecting group. The time and duration over which an active substance is released can be controlled. The invention also relates to a process for the preparation of such a composition and to a process for the controlled release of the active substance

Composition consisting of a dendrimer and an active substance

The invention relates to a composition consisting of a dendrimer provided with blocking agents and an active substance occluded in the dendrimer. According to the invention a blocking agent is a compound which is sterically of sufficient size, which readily enters into a chemical bond with the terminal groups of a dendrimer and which can also be split off from the dendrimer or be modified without thereby affecting the chemical structure of the dendrimer and the active substance. The blocking agent can be provided with protective groups. Such conjugates have the advantage that the time at which the releasing of the active substance starts, can be controlled. The invention also relates to a process for the preparation of such a composition and to a process for the controlled release of the active substance

Process for the preparation of a dendritic macromolecule

The invention relates to a process for the preparation of a dendritic macromolecule, wherein an amount of a core molecule comprising at least one functional group is dissolved in a solvent, after which alternatingly an addition reaction and a hydrogenation reaction are carried out, during the addition reaction vinyl cyanide units being added to the solution which react with the functional groups in such a manner that a dendritic macromolecule with terminal cyanide groups is formed, and during the hydrogenation reaction the cyanide groups being reduced in solution by means of hydrogen and a suitable catalyst in such a manner that functional amine groups are formed, wherein the solvent in which the hydrogenation reaction takes place is an alcohol which contains an amount of ammonia, the molar ratio between the amount of ammonia and the number of cyanide groups being higher than 0.8

Synthesis of 8-, 9-, 12-, and 13-mono-13C-retinal

Bio-organic Synthesi

Poor sporting abilities after tibial plateau fractures involving the posterior column: how can we do better?

Purpose: Tibial plateau fractures with the involvement of the posterior column are an important prognostic factor towards poor functional outcome. We aimed to assess the sporting abilities postoperatively with special emphasis on the type of sports and sport-specific movements, as well as time needed to resume sports, restricting factors in sports engagement, and patient satisfaction. We aimed to provide prognostic information on return to sports. Methods: Demographic, clinical and radiological variables were retrospectively collected from 82 multicentric patients between 2014 and 2016. Prospectively, sporting abilities before and after surgery were determined using questionnaires at a mean follow-up of 33 months postoperatively. Results: Involvement in sports significantly decreased, with only 68.4% of patients resuming sports (p < 0.001). The mean time needed to partially or fully resume sports was 6–9 and 9–12 months, respectively. The ability to resume at the pre-injury level of effort and performance was 22% and 12%, respectively. Restricting factors were pain (66%), fear of re-injury (37%), limited range of motion (26%), and instability (21%). The majority (59%) of patients were unsatisfied with their physical abilities. Significantly worse outcomes were observed in patients playing high-impact sports, experiencing knee pain during physical activity, suffering from extension/valgus or flexion/varus trauma. Conclusions: Tibial plateau fractures with the involvement of the posterior column significantly hamper the patients’ sporting abilities, leaving the majority of patients unsatisfied. Preoperative counseling about prognosis, setting realistic expectations, optimizing rehabilitation and pain management postoperatively, and advising low-impact sports might improve engagement in physical activities and emotional impact on patients. Level of evidence: 3

Dendritic macromolecule and the preparation thereof

The invention relates to a dendritic macromolecule comprising a core and branches emanating from the core wherein the branches are based on vinyl cyanide and/or fumaryl dinatrile units. The invention also relates to processes for preparing these dendritic macromolecules. The dendritic macromolecules according to the invention are not sensitive to degradation through hydrolysis reactions and are also very stable at a high temperature. The processes are very suitable for large scale production of the dendritic macromolecules without requiring purification of reaction intermediates

Hematopoietic stem cell transplantation in a patient with proteasome-associated autoinflammatory syndrome (PRAAS)

Background: Proteasome-associated autoinflammatory syndromes (PRAASs) form a family of recently described rare autosomal recessive disorders of disturbed proteasome assembly and proteolytic activity caused by mutations in genes coding for proteasome subunits. The treatment options for these proteasome disorders consist of lifelong immunosuppressive drugs or Janus kinase inhibitors, which may have partial efficacy and noticeable side effects. Because proteasomes are ubiquitously expressed, it is unknown whether hematopoietic stem cell transplantation (HSCT) may be a sufficient treatment option. Objective: Our aim was to report the case of a young boy with a treatment-resistant cutaneous vasculitis that was initially suspected to be associated with a gene variant in SH2D1A. Methods: Whole-exome sequencing was performed to identify the genetic defect. Molecular and functional analyses were performed to assess the impact of variants on proteasomal function. The immune characterization led to the decision to perform HSCT on our patient and conduct follow-up over the 7-year period after the transplant. Because loss of myeloid chimerism after the first HSCT was associated with relapse of autoinflammation, a second HSCT was performed. Results: After the successful second HSCT, the patient developed mild symptoms of lipodystrophy, which raised the suspicion of a PRAAS. Genetic analysis revealed 2 novel heterozygous variants in PSMB4 (encoding proteasomal subunit beta 7). Retrospective analysis of patient cells stored before the first HSCT and patient cells obtained after the second HSCT demonstrated that HSCT successfully rescued proteasome function, restored protein homeostasis, and resolved the interferon-stimulated gene signature. Furthermore, successful HSCT alleviated the autoinflammatory manifestations in our patient. Conclusion: Patients with treatment-resistant PRAAS can be cured by HSCT.Transplantation and immunomodulatio

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d