Specificity of the effect of polyunsaturated phosphatidylcholine depending on mode of administration and species of animal

Research Institute of Physicochemical Medicine, Ministry of Health of the RSFSR, Moscow. Institute of Clinical Chemistry and Laboratory Diagnosis, Karl Marx University, Leipzig, East Germany. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 55–58, January, 1992.     

Population screening on a population level in Leipzig within the scope of the Bavarian cholesterol project]

Cholesterol determinations of 15.391 inhabitants of Leipzig were carried out in November 1990 within the Bavarian Cholesterol-Screening-Project. The aim of this screening on population basis was to identify individuals with elevated blood cholesterol levels as one of the risk factors of atherosclerosis. Capillary blood cholesterol was measured by means of the Reflotron dry-chemistry system (Boehringer, Mannheim). 27% of the inhabitants of Leipzig show cholesterol levels lower than 5.2 mmol/l as recommended by the European Society of Atherosclerosis Research. Furthermore the characteristic age dependence is seen. In comparison with the town Nürnberg lower mean cholesterol values were found in Leipzig.     

PLGA-PEG-PLGA tri-block copolymers as in situ gel-forming peptide delivery system: effect of formulation properties on peptide release

Various controlled peptide and protein delivery systems have been investigated for their potential for treatment of chronic diseases. In situ gelling systems are very attractive due to their biocompatibility, biodegradability, and simple manufacturing processes. The objective of this work was to investigate the effect of different excipients on release profile of calcitonin as a model protein from PLGA-PEG-PLGA thermally reversible gels. PLGA-PEG-PLGA with the ratio of PLGA to PEG equal to 2.5 was synthesized and characterized by (1)H NMR and gel permeation chromatography (GPC). The PLGA-PEG-PLGA polymeric solutions (25% w/w) containing calcitonin (0.05% w/w) and other excipients in various concentrations were prepared, and drug release from the thermally reversible gels was evaluated. It was shown that drug release from the systems was dramatically reduced when PEG 200 or PEG 1000 was added to the systems. This may be due to the effect of PEG as an internal cross-linking agent or the formation of PEG complexes that decrease the rate of drug release. Sodium laurel sulfate (SLS) was also shown to reduce the rate of drug release from the systems. This may be due to the large ionic heads of SLS that attract counterions of calcitonin. It can be concluded that the drug release rate from the systems can be controlled by using different excipients.     

A theoretical study on interactions between mitoxantrone as an anticancer drug and DNA: application in drug design

This research is an effort to further understand the physicochemical interaction between the novel drug, mitoxantrone (MTX) and its biologic receptor, DNA. The ultimate goal is to design drugs that interact more with DNA. Understanding the physicochemical properties of the drug as well as the mechanism by which it interacts with DNA, it should ultimately allow the rational design of novel anti-cancer or anti-viral drugs. Molecular modelling on the complex formed between MTX and DNA presented that this complex was indeed fully capable of participating in the formation of a stable intercalation site. Furthermore, the molecular geometries of MTX and the DNA bases (adenine, guanine, cytosine and thymine) were optimized with the aid of the B3LYP/6-31G* method. The properties of the isolated intercalator and its stacking interactions with the adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were studied with the DFTB method (density functional tight-binding), an approximate version of the DFT method, that was extended to cover the London dispersion energy. The B3LYP/6-31G* stabilization energies of the intercalator...base pair complexes were found 10.06 kcal/mol and 21.64 kcal/mol for AT...MTX and GC...MTX, respectively. It was concluded that the dispersion energy and the electrostatic interaction contributed to the stability of the intercalator.DNA base pair complexes. The results concluded from the comparison of the DFTB method and the Hartree-fock method point out that these methods show close results and support each other.     

In vitro and in vivo investigation of a novel amniotic‐based chitosan dressing for wound healing

It is more than a decade that amniotic membrane has been used as a wound dressing because of its anti‐inflammatory, anti‐microbial, anti‐fibrotic, anti‐scarring properties, as well as its pain relieving and epithelialization promoting features. However, amniotic membrane had limited applications because it needs to suture in surgery, is highly fragile, firmly adhere to the wound and may cause bleeding and pain when changing the bandage. This study investigated the possibility of development of a novel amniotic‐based chitosan gel dressing as a potential wound repair substrate with marked efficacy. In this experiment, amniotic gel prepared based on chitosan/PVP gel containing human amniotic membrane extract (AME‐Gel) was investigated in terms of wound‐healing efficacy and scar preventive effects in a rat burn model. The levels of re‐epithelialization and dermal regeneration were examined by histological assessment using H&E and Masson's trichrome staining. Also, we clarified the mechanism of healing and cytokine‐releasing activities of AME as well as its effect on epithelization, angiogenesis, and fibroblast growth and migration. Our results revealed that AME‐Gel induces epidermal and dermal regeneration at a shorter time through formation of granulation tissue, enhancement of fibroblast proliferation, and improvement of blood capillary formation concomitant with developing collagen bundles. Therefore, AME‐Gel could be considered a simple and easy to be used as a biological dressing for any type of superficial burn wounds, without any adverse effects.     

Impact and Epidemiological Investigations into the Incursion and Spread of Peste des Petits Ruminants in the Comoros Archipelago: An Increased Threat to Surrounding Islands

Late October 2012, a great number of deaths of unknown origin occurred in goat herds in the suburbs of Ngazidja, located in the Comoros archipelago. Few weeks later, laboratory testing requested by the animal health authorities resulted in the identification of peste des petits ruminants (PPR) infection. Notably, the Index case could be attributed to a sick goat imported from Tanzania. Viral isolation was successful from the lungs leading to the whole N nucleoprotein gene sequencing. Phylogenetic analysis revealed that the strain belongs to the lineage III which includes strains of eastern African origin. In addition, to evaluate the impact of PPR on the Comorian indigenous domesticated ruminant population, a cross‐sectional PPR serological survey was conducted between April and July 2013. A low overall PPRV antibody prevalence 2.24% (95% CI [1.38; 3.08]) was detected with a Grande Comore prevalence of 3.34% (IC = [2.09; 4.63]) with a limited spread of the disease mainly due to farm practices such as limited contacts between farm animals and rapid slaughtering of sick animals.     

Novel biotinylated chitosan-graft-polyethyleneimine copolymer as a targeted non-viral vector for anti-EGF receptor siRNA delivery in cancer cells

The major impediments to develop an efficient non-viral siRNA-mediated gene silencing method, as a therapeutic approach, are the low cellular uptake and intracellular delivery and release of non-viral vectors. To overcome these problems, designing a proper vector with high transfection efficiency is obviously under scrutiny of various studies. The present study, evaluate a novel biotinylated chitosan-graft-polyethyleneimine (Bio-Chi-g-PEI) copolymer as an appropriate non-viral vector for targeted delivery of siRNA to cancer cells. The composition of the synthesized Bio-Chi-g-PEI copolymer was thoroughly characterized using ¹H NMR and FTIR spectroscopy, besides the hydroxyazobenzene-2-carboxylic acid (HABA) assay. In vitro cytotoxicity assay of the Bio-Chi-g-PEI copolymers was performed by MTT assay. Cytotoxicity evaluations indicated that the new copolymer was markedly less toxic than PEI 25KD. Physicochemical properties of the Bio-Chi-g-PEI/siRNA complexes such as complex stability, size, zeta potential, and their morphology at various weight ratios, investigated by appropriate methods, revealed the suitability of the complexes for the transfection. The efficient cellular internalization of the complexes for HeLa and OVCAR-3 cells in culture media was confirmed by intracellular tracking of the prepared complexes using confocal laser scanning microscopy and Cy3-labeled anti-epidermal growth factor receptor siRNA. Finally, evaluation of the transfection efficiency and gene silencing by flow cytometry and real-time polymerase chain reaction highlighted the significantly higher efficiency of transfection and silencing for biotinylated copolymer compared with the PEI 25KD and non-biotinylated copolymer.     

Physicochemical and Biological Characterization of Pep‐1/Elastin Complexes

Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell‐penetrating peptides have been studied to increase the penetration of therapeutic proteins into and through the skin. Cell‐penetrating peptides facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a cell‐penetrating peptide called Pep‐1. As the biophysical characteristics of cell‐penetrating peptide/protein complexes have been linked with their biological responses, in this study, we investigated biophysical properties of Pep‐1/elastin complexes (ratio 10:1) stored in three temperatures (?20 °C, 4 °C and 25 °C) by photon correlation spectroscopy, circular dichroism and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In‐Vivo FX Pro Imaging System.     

Formulation and evaluation of an in situ gel forming system for controlled delivery of triptorelin acetate

The novel physical hydrogels composed of chitosan or its water soluble derivatives such as carboxymethyl chitosan (CMCh) and sodium carboxymethyl chitosan (NaCMCh) and opened ring polyvinyl pyrrolidone (OP-PVP) were used as a controlled delivery system for triptorelin acetate, a luteinizing-releasing hormone agonist. The in situ gel forming system designed according to physical interactions such as chains entanglements and hydrophilic attractions especially h-bonds of chitosan and/or NaCMCh and OR-PVP. In order to increase in situ gel forming rate the chitosan microspheres prepared through spray drying technique. The chitosan or NaCMCh/OR-PVP blends prepared at different ratios (0.05, 0.10, 0.12, 0.16, 0.20 and 0.24) and suspended in sesame oil as non-aqueous vehicle at different solid content (10-30%). The suitable ratio of polymers with faster in situ gel forming rate was selected for in vivo studies. The gel formation and drug release from the system was evaluated both in vitro and in vivo. In vitro and in vivo results were compared with Diphereline SR 3.75mg, a commercially available controlled delivery system of triptorelin. In vitro release studies showed a sustained release profile for about 192h with first order kinetics. In vivo studies on male rats by determination of serum testosterone were confirmed the acceptable performance of in situ gel forming system compared with Diphereline SR in decreasing the serum testosterone level for 35days, demonstrating the potential of the novel in situ gel forming system for controlled delivery of peptides.