Визначення гострої та підгострої токсичності препарату “Тиловет 20 %”

The article presents the results of determination of acute and subacute toxicity of the drug “Tilovet 20 %”, which was made on the basis of tylosin tartrate. In result of the conducted researches, it was found out, that LD50 of the drug “Tilovet 20 %” by intramuscular injection to white mice (calculated by the method of G. Kerber) is 10000 and mg/kg, and for white rats – 9583.33 mg/kg. Long-term use of the drug in a therapeutic dose caused a tendency to the decrease of hemoglobin concentration, amount of erythrocytes, platelets, hematocrit value, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), content of the total protein, creatinine level, ALP activity on the background of a slight an increase of amount of leukocytes, urea level, AST and ALT activity compared to the values of the control group. The use of the drug in a dose that is 10 times higher than the therapeutic, caused a probable decrease of hemoglobin concentration by – 6.6 % (P < 0.05), platelet count by – 32.5 % (P < 0.05), mean corpuscular hemoglobin (MCH) by – 4.2 % (P < 0.05), mean corpuscular hemoglobin concentration (MCHC) by – 1.5 % (P < 0.1), hematocrit value by – 4.95 %, and total protein content by – 10.7 % (P < 0.05), on the background of a slight an increase of amount of leukocytes by 5.3 %, ALP activity by – 17.5 %, compared to the values oft he control group. Therefore, all of the above may indicate to the suppression of hematopoietic processes and a decrease in the protein-synthesizing function of the liver.У статті наведені результати вивчення гострої та підгострої токсичності препарату “Тиловет 20 %”, виготовленого на основі тилозину тартрат. У результаті проведених досліджень було встановлено, що LD50 препарату “Тиловет 20 %” за внутрішньом’язового введення білим мишам (обчислення за методом Г. Кербера) становить 10000 та мг/кг, а для білих щурів – 9583,33 мг/кг. Довготривале застосування препарату у терапевтичній дозі викликало тенденцію до зниження концентрації гемоглобіну, кількості еритроцитів, тромбоцитів, величини гематокриту, середнього вмісту гемоглобіну в еритроциті (МСН), середнього об’єму еритроцита (МСV), вмісту загального білка, рівня креатиніну, активності ЛФ на тлі незначного зростання кількості лейкоцитів, рівня сечовини, активності АсАТ та АлАТ порівняно з величинами контрольної групи. Застосування препарату у дозі, яка в 10 разів перевищує терапевтичну, викликало вірогідне зниження концентрації гемоглобіну на 6,6 % (Р < 0,05), кількості тромбоцитів – на 32,5 % (Р < 0,05), середнього вмісту гемоглобіну в еритроциті (МСН) – на 4,2 % (Р < 0,05), середньої концентрації гемоглобіну в еритроциті (МСНС) – на 1,5 % (Р < 0,01), величини гематокриту – на  4,95 % та вмісту загального білка – на 10,7 % (Р < 0,05) на тлі незначного зростання кількості лейкоцитів на 5,3 %, активності ЛФ – на 17,5 % порівняно з величинами контрольної групи. Отже, усе вищевказане може свідчити про пригнічення процесів  кровотворення та зниження протеїнсинтезувальної функції печінки

The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?

International audienceIn most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs migh confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1

1.2 A resolution crystal structure of Escherichia coli WrbA holoprotein

Acta Crystallographica Section D: Biological Crystallography. Volume 69, Issue 9, September 2013, Pages 1748-1757.The Escherichia coli protein WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase, was crystallized under new conditions in the presence of FAD or the native cofactor FMN. Slow-growing deep yellow crystals formed with FAD display the tetragonal bipyramidal shape typical for WrbA and diffract to 1.2Å resolution, the highest yet reported. Faster-growing deep yellow crystals formed with FMN display an atypical shape, but diffract to only ∼1.6Å resolution and are not analysed further here. The 1.2Å resolution structure detailed here revealed only FMN in the active site and no electron density that can accommodate the missing parts of FAD. The very high resolution supports the modelling of the FMN isoalloxazine with a small but distinct propeller twist, apparently the first experimental observation of this predicted conformation, which appears to be enforced by the protein through a network of hydrogen bonds. Comparison of the electron density of the twisted isoalloxazine ring with the results of QM/MM simulations is compatible with the oxidized redox state. The very high resolution also supports the unique refinement of Met10 as the sulfoxide, confirmed by mass spectrometry. Bond lengths, intramolecular distances, and the pattern of hydrogen-bond donors and acceptors suggest the cofactor may interact with Met10. Slow incorporation of FMN, which is present as a trace contaminant in stocks of FAD, into growing crystals may be responsible for the near-atomic resolution, but a direct effect of the conformation of FMN and/or Met10 sulfoxide cannot be ruled out. © 2013 International Union of Crystallography Printed in Singapore-all rights reserved