The polymorphism of statins and its effect on their physicochemical properties.

Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their pharmacological activity. Solid dosage forms may exist in both crystalline and amorphous forms. Amorphous varieties are characterized by higher solubility and dissolution rates, while crystalline forms show greater purity and storage stability. The choice between the crystalline or amorphous form of a drug is extremely important to ensure effective and safe pharmacotherapy. Statins - the most commonly used group of drugs in the treatment of lipid disorders - are an example of drugs that occur in many crystalline and amorphous forms. Statins belong to class II in the biopharmaceutical classification system (BCS), which means that they are poorly soluble, but permeate biological membranes well. The bioavailability of statins shows considerable variation, which is associated with the first-pass effect in the liver and the accumulation of the drug in the hepatocytes. The improvement of bioavailability after oral administration of poorly soluble medicinal substances remains one of the most challenging aspects of the drug development process. A specific polymorphic form is obtained by applying appropriate conditions during the process of its preparation under industrial conditions, including the use of a suitable solvent, a specific temperature or rate of crystallization. The article provides a comprehensive update on the current knowledge of the influence of polymorphic form on statin solubility and bioavailability. Research is still being carried out to obtain new polymorphic varieties of statins that are characterized by better physicochemical and pharmacokinetic parameters.

The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors.

Although anti-human leukocyte antigen antibodies (anti-HLA Abs) are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.

Transposition of a 600 thousand-year-old LTR retrotransposon in the model legume Lotus japonicus.

We have identified a new Ty3-gypsy retrotransposon family named LORE2 (Lotus retrotransposon 2) and documented its activity in the model legume Lotus japonicus. Three new LORE2 insertions were found in symbiotic mutant alleles isolated from a plant population, established by tissue culture mediated transformation of the L. japonicus Gifu accession. Low transcriptional and transpositional activities of LORE2 in cultured cells suggested that the LORE2 transpositions identified in the three symbiotic mutants occurred in intact plants, not in callus. Tracing of the transpositional events identified two active LORE2 members in Gifu. One of them named LORE2A possesses a deletion in its coding region and polymorphisms between intraelemental LTRs. LORE2A is thus an aged element, estimated as 600 thousand years old. Our findings indicate that plant genomes carry more cryptic LTR retrotransposons, i.e., aged yet active, than estimated before, and that these cryptic elements may have contributed to plant genome dynamics, for example, the burst of transpositions reported in several plant species.