A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

Aims: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients.

Comparative pharmacokinetics of nalbuphine nasal spray and solution for injection in healthy volunteers.

Aims: Nalbuphine is a synthetic opioid with comparable analgesic activity to morphine but with a better safety profile. Nalbuphine is only available in injectable form due to low oral bioavailability. Nasal nalbuphine spray provides advantages in drug safety, avoids hepatic first-pass metabolism, is non-invasive and is convenient for patient-controlled analgesia by self-administration.

Identification of promising alfalfa varieties in conditions of the southern forest-steppe zone (Republic of Bashkortostan): a study of economic and biological characteristics.

Background: Alfalfa (Medicago sativa L.) is one of the most important forage crops, but its seed productivity varies from year to year due to weather conditions. Alfalfa is a forage crop rich in nutrients which makes it valuable.

A facile and sensitive HPLC-MS/MS method for quantification of 3,3'-diindolylmethane in plasma samples.

Indole-3-carbinol is the subject of ongoing biomedical research owing to its potential antiatherogenic, anticarcinogenic and antioxidant effects. The antitumor properties are mainly associated with its major metabolite, i.e.

Synthesis, Self-Assembly and In Vitro Cellular Uptake Kinetics of Nanosized Drug Carriers Based on Aggregates of Amphiphilic Oligomers of -Vinyl-2-pyrrolidone.

Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier-membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of -vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD).

Can ionic concentration changes due to mechanical deformation be responsible for the neurostimulation caused by focused ultrasound? A simulation study.

Ultrasound stimulation is an emerging neuromodulation technique, for which the exact mechanism of action is still unknown. Despite the number of hypotheses such as mechanosensitive ion channels and intermembrane cavitation, they fail to explain all of the observed experimental effects. Here we are investigating the ionic concentration change as a prime mechanism for the neurostimulation by the ultrasound.

Сase Report of Acute Toxic Imatinib-induced Hepatitis in a Patient with Chronic Myeloid Leukemia, Sulfa Allergy, and Rheumatoid Arthritis.

The introduction of imatinib has substantially changed the approaches to the therapy of chronic myeloid leukemia. However, this drug can cause hepatic failure and death in rare cases. This report describes a clinical case of acute, toxic imatinib-induced hepatitis in a 56-year-old woman with chronic myeloid leukemia and concomitant sulfa allergy and rheumatoid arthritis.

Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk -Not-Amplified Human Neuroblastoma.

High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease, including a focus on tumor-infiltrating lymphocytes (TIL).

First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN).

Background: Targeted pharmacological correction is used extensively in medical practice today. 3,3'-Diindolylmethane (DIM) is known as a substance with various anticancer properties. An interim study of the efficacy of a new drug Infemin on the basis of diindolylmethane (DIM) with improved bioavalability has been conducted.

Identification of non-random sequence properties in groups of signature peptides obtained in random sequence peptide microarray experiments.

Immunosignaturing is an emerging experimental technique that uses random sequence peptide microarrays to detect antibodies produced by the immune system in response to a particular disease. Two important questions regarding immunosignaturing are "Do microarray peptides that exhibit a strong affinity to a given type of antibodies share common sequence properties?" and "If so, what are those properties?" In this work, three statistical tests designed to detect non-random patterns in the amino acid makeup of a group of microarray peptides are presented. One test detects patterns of significantly biased amino acid usage, whereas the other two detect patterns of significant bias in the biochemical properties.

Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane's efficacy and safety in the treatment of CIN: implications for cervical cancer prevention.

Background: The article presents the results of a clinical trial on the efficacy and safety of a novel pharmaceutical composition in the form of vaginal suppositories containing diindolylmethane in the course of cervical intraepithelial neoplasia (CIN) I-II conservative treatment. It offers an attractive drug therapy for more personalized prevention of cervical cancer.

Methods: A total of 78 women of reproductive age were included.

PR2ALIGN: a stand-alone software program and a web-server for protein sequence alignment using weighted biochemical properties of amino acids.

Background: Alignment of amino acid sequences is the main sequence comparison method used in computational molecular biology. The selection of the amino acid substitution matrix best suitable for a given alignment problem is one of the most important decisions the user has to make. In a conventional amino acid substitution matrix all elements are fixed and their values cannot be easily adjusted.

Safety and tolerability of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN).

Background: It has been shown previously that novel formulation of 3,3'-diindolylmethane (DIM) substance with high bioavailability (Infemin) inhibits tumor development due to the tumor growth rate reduction in the xenograft model of prostate cancer. Prostatic intraepithelial neoplasia (PIN) is considered to be promising as a personalized and preventive treatment strategy of prostate cancer (PC). We assessed the safety of Infemin in men with PIN and discussed the interim results.

Comparative preclinical pharmacokinetics study of 3,3'-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon?

Background: 3,3'-Diindolylmethane (DIM) is known as an agent of natural origin that provides protection against different cancers due to the broad spectrum of its biological activities in vivo. However, this substance has a very poor biodistribution and absorption in animal tissues. This preclinical trial was conducted to evaluate the pharmacokinetics and bioavailability of various DIM formulations in animal model.

Brownian nanoimaging of interface dynamics and ligand-receptor binding at cell surfaces in 3-D.

We describe a method for nanoimaging interfacial dynamics and ligand-receptor binding at surfaces of live cells in 3-D. The imaging probe is a 1-μm diameter glass bead confined by a soft laser trap to create a "cloud" of fluctuating states. Using a facile on-line method of video image analysis, the probe displacements are reported at ~10 ms intervals with bare precisions (±SD) of 4-6 nm along the optical axis (elevation) and 2 nm in the transverse directions.

Protein sequence alignment with family-specific amino acid similarity matrices.

Background: Alignment of amino acid sequences by means of dynamic programming is a cornerstone sequence comparison method. The quality of alignments produced by dynamic programming critically depends on the choice of the alignment scoring function. Therefore, for a specific alignment problem one needs a way of selecting the best performing scoring function.

Analysis of actin FLAP dynamics in the leading lamella.

Background: The transport of labeled G-actin from the mid-lamella region to the leading edge in a highly motile malignant rat fibroblast line has been studied using fluorescence localization after photobleaching or FLAP, and the transit times recorded in these experiments were so fast that simple diffusion was deemed an insufficient explanation (see Zicha et al., Science, v. 300, pp.

Simplified computational methods for the analysis of protein flexibility.

Conformational flexibility is an inherent property of the protein structure. Large scale changes in the protein conformation play a key role in a variety of fundamental biological activities and have been implicated in a number of diseases. The time scales of functionally relevant dynamic processes in proteins generally do not allow the researchers to study them by the means of detailed atomic level simulations.

A web server for inferring the human N-acetyltransferase-2 (NAT2) enzymatic phenotype from NAT2 genotype.

Unlabelled: N-acetyltransferase-2 (NAT2) is an important enzyme that catalyzes the acetylation of aromatic and heterocyclic amine carcinogens. Individuals in human populations are divided into three NAT2 acetylator phenotypes: slow, rapid and intermediate. NAT2PRED is a web server that implements a supervised pattern recognition method to infer NAT2 phenotype from SNPs found in NAT2 gene positions 282, 341, 481, 590, 803 and 857.

FlexPred: a web-server for predicting residue positions involved in conformational switches in proteins.

Unlabelled: Conformational switches observed in the protein backbone play a key role in a variety of fundamental biological activities. This paper describes a web-server that implements a pattern recognition algorithm trained on the examples from the Database of Macromolecular Movements to predict residue positions involved in conformational switches. Prediction can be performed at an adjustable false positive rate using a user-supplied protein sequence in FASTA format or a structure in a Protein Data Bank (PDB) file.

CFP: a web-server for constructing sequence-based protein conformational flexibility profiles.

Unlabelled: Many proteins contain conformationally flexible segments that undergo significant changes in the backbone conformation or completely lack a well-defined conformation. Previously, we have developed the generalized local propensity (GLP), a quantitative sequence-based measure of the protein backbone flexibility. In this paper, we present the CFP (Conformational Flexibility Profile) web-server that constructs the GLP flexibility profile for a user-submitted sequence and uses this profile to identify segments with high backbone flexibility.

On the Accuracy of Sequence-Based Computational Inference of Protein Residues Involved in Interactions with DNA.

Methods for computational inference of DNA-binding residues in DNA-binding proteins are usually developed using classification techniques trained to distinguish between binding and non-binding residues on the basis of known examples observed in experimentally determined high-resolution structures of protein-DNA complexes. What degree of accuracy can be expected when a computational methods is applied to a particular novel protein remains largely unknown. We test the utility of classification methods on the example of Kernel Logistic Regression (KLR) predictors of DNA-binding residues.