Evaluation of the Efficiency and Safety of Anaferon (Pediatric Formulation) in the Treatment of Chickenpox in Children

Addition of anaferon (pediatric formulation) to the therapy of chickenpox patients led to more rapid disappearance of the main symptoms and alleviated the course of the disease. The safety of the preparation is confirmed by the absence of undesirable events and stability of laboratory indexes against the background of therapy.     

Non-coding RNA as a trigger of neuropathologic disorder phenotypes in transgenic Drosophila

At most, many protein-misfolding diseases develop as environmentally induced sporadic disorders. Recent studies indicate that the dynamic interplay between a wide repertoire of noncoding RNAs and the environment play an important role in brain development and pathogenesis of brain disorders. To elucidate this new issue, novel animal models which reproduce the most prominent disease manifestations are required. For this, transgenic Drosophila strains were constructed to express small highly structured, non-coding RNA under control of a heat shock promoter. Expression of the RNA induced formation of intracellular aggregates revealed by Thioflafin T in embryonic cell culture and Congo Red in the brain of transgenic flies. Also, this strongly perturbed the brain control of locomotion monitored by the parameters of sound production and memory retention of young 5-day-old males. This novel model demonstrates that expression of non-coding RNA alone is sufficient to trigger neuropathology.     

Modelling and expression studies of two novel mutations causing factor V deficiency

Human coagulation factor V (FV), a non-enzymatic cofactor of the prothrombinase complex, is required for the rapid generation of thrombin. FV deficiency is a rare autosomal recessive bleeding disorder. We describe two novel mutations, Tyr91Asn and Asp2098Tyr, found in two probands with a residual FV activity of 51% and 4%, respectively. Modelling and structural analysis of these mutations were performed following short-duration molecular dynamics (MD) simulation. Asp2098Tyr lead to abolishment of the highly conserved salt bridge Asp2098-Arg2171 presumably required for structural integrity of the C2 domain. MD studies suggest that additional conformational changes resulting from this mutation involve local rearrangements at Tyr2063 and Tyr2064 and so affect the phospholipid-membrane binding. MD modelling of the Try91Asn mutant revealed a conformational change nearby the Cu(2+) binding site that could affect overall stabilization of the heavy and light chains. These findings suggest that both mutations influence the structural integrity of FV protein. Transient expression data of wild-type and mutant FV variants in 293T human embryonic kidney cells showed FV-specific activity reduced to 26% for Asp2098Tyr and 56% for Tyr91Asn compared to that of wild-type. Thus, both the data from the short duration molecular dynamic simulation and from expression analysis indicate alterations of the FV protein variants that explain the clinical phenotype.     

Synthesis of Betulinic Acid from Betulin Extract and Study of the Antiviral and Antiulcer Activity of Some Related Terpenoids

Pharmaceutical Chemistry Journal -     

Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.      

Effectiveness of lamivudine in the treatment of chronic HBeAg-negative viral hepatitis B: results of continuous therapy for 18 months

The efficacy of monotherapy with one of the analogues of synthetic nucleosides (lamivudine) was studied in 22 patients with chronic viral hepatitis B (CVHB). The specific feature of the selected group was that there was no serum HBeAg, which is usually regarded as a sign of viral mutation. The time course of changes in the activity of blood and hepatic inflammatory processes and viral replication were studied at equal intervals. There was a direct correlation between the suppression of viral replication and the regression of activity indices, such as ALT, serological markers, DNA of viral hepatitis B, and the morphological constituents of the Knodell index) during lamivudine therapy. However, there were no substantial changes in the parameters of fibrosis throughout the treatment. Therapy resistance was revealed in 3 of the 22 patients with CVHV. Its basis was the mutation of hepatitis B virus in the YMDD-motive, which was detected in 2 of the 3 patients.     

Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations

One of the most common and unwanted side effects during oral anticoagulant therapy (OAT) is bleeding complications. In rare cases, vitamin K antagonist (VKA)-related bleeding events are associated with mutations affecting the F9 propeptide at amino acid position 37 due to a substitution of alanine to either valine or threonine. Based on our actual cohort of 18 patients, we update the knowledge on this rare phenotype and its origin. A founder mutation for both variants was reconfirmed by haplotype analysis of intronic and extragenic short tandem repeat (STR) polymorphisms with a higher prevalence in Switzerland than in other regions of Europe. Screening of healthy individuals for the presence of these F9 gene mutations did not identify any of these variants, thus proving the rare occurrence of this genotype. Furthermore, both variants were expressed in vitro and warfarin dose responses were studied. Our warfarin dose response analysis confirmed higher sensitivity of both variants to warfarin with the effect being more apparent for Ala37Thr. Thus, although F9 propeptide mutation-associated hypersensitivity to VKA is a rare phenomenon, awareness towards this bleeding phenotype is important to identify patients at risk.     

预断溃疡性结肠炎自然史的可能性

在提高炎症性肠病(1BD)疗效的同时,因治疗产生的毒性也可能增加,因此筛选出高危患者尤为重要.我们首先需要确定与溃疡性结肠炎(UC)自然史最为相关的临床终点事件,然后明确能预测严重后果的危险因素.