Experimental study of the pharmacokinetics of an amphotericin B derivative

Absorption, distribution and excretion of a new water soluble derivative of amphotericin B (NWSDA) were studied after its administration by different routes. After the antibiotic intravenous administration the therapeutic concentrations in blood, organs and urine were shown to remain for prolonged periods. The likely sites of NWSDA deposition were detected with microbiological and radionuclide methods. The most prolonged periods of antibiotic preservation were stated in the renal cortex, spleen and lungs. The ways of NWSDA excretion were studied in operated animals. Only 3.5 per cent of the antibiotic was excreted with urine and bile for 24 hours. The pharmacokinetic parameters of NWSDA after its intravenous administration were estimated. The bioavailability of the antibiotic after its intramuscular and oral administration was found to be low.     

Makeup and properties of E. coli cells with a varying level of resistance to tetracycline]

Lipopolysaccharide composition of tetracycline sensitive and resistant strains of E. coli was studied comparatively. It was shown that that resistance of E. coli to tetracycline was probably due to the differences in the lipopolysaccharide component composition of the outer membrane. On the basis of the activity comparison of the Mg2+- and Ca2+-activated ATP-ase of the membrane fraction of the tetracycline sensitive and resistance strains of E. coli it was concluded that the resistance development in the strains tested to tetracycline was not associated with the changes in the ATP-ase activity.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

Transformation of Internal Extracellular Bacteria Isolated from Rhagoletis completa Cresson Gut with Enhanced Green Fluorescent Protein

We discovered Zeocin™ is an effective antibiotic against Enterobacter agglomerans and Klebsiella pneumoniae strains isolated from the walnut husk fly (Rhagoletis completa Cresson: Family Tephritidae) and that bleomycin resistance can be used as a selective marker in transforming plasmids. We transformed Ent. agglomerans and K. pneumoniae strains originally isolated from their close association with R. completa gut to produce enhanced green fluorescent protein, a variant of green fluorescent protein in the first demonstration of genetic transformation of internal extracellular bacteria isolated from a tephritid pest. We report methods for plasmid-mediated transformation of these bacteria, the expression of fluorescent marker protein from the transforming plasmids, and the stability of the transforming plasmid in the bacteria. We also discuss applications of this technology in the study of pest biology and control implementation. Received: 5 November 1999 / Accepted: 15 December 1999     

Ubiquinone and carotene production in the <Emphasis Type="Italic">Mucorales Blakeslea</Emphasis> and <Emphasis Type="Italic">Phycomyces</Emphasis>

The filamentous fungi Phycomyces blakesleeanus and Blakeslea trispora (Zygomycota, Mucorales) are actual or potential industrial sources of β-carotene and lycopene. These chemicals and the large terpenoid moiety of ubiquinone derive from geranylgeranyl pyrophosphate. We measured the ubiquinone and carotene contents of wild-type and genetically modified strains under various conditions. Light slightly increased the ubiquinone content of Blakeslea and had no effect on that of Phycomyces. Oxidative stress modified ubiquinone production in Phycomyces and carotene production in both fungi. Sexual interaction and mutations in both organisms made the carotene content vary from traces to 23 mg/g dry mass, while the ubiquinone content remained unchanged at 0.3 mg/g dry mass. We concluded that the biosyntheses of ubiquinone and carotene are not coregulated. The specific regulation for carotene biosynthesis does not affect even indirectly the production of ubiquinone, as would be expected if terpenoids were synthesized through a branched pathway that could divert precursor flows from one branch to another.     

Variants in the interleukin-1 alpha and beta genes,and the risk for periodontal disease in dogs

Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria. In humans, polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case–control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A >C and IL1A/1_g.521T >A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03–0.76), P= 0.022; 5.76 (1.03–32.1), P= 0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G >T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines.     

How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS

Development of the segmented central nerve cords of vertebrates and invertebrates requires connecting successive neuromeres. Here, we show both how a pathway is constructed to guide pioneer axons between segments of the Drosophila CNS, and how motility of the pioneers along that pathway is promoted. First, canonical Notch signaling in specialized glial cells causes nearby differentiating neurons to extrude a mesh of fine projections, and shapes that mesh into a continuous carpet that bridges from segment to segment, hugging the glial surface. This is the direct substratum that pioneer axons follow as they grow. Simultaneously, Notch uses an alternate, non-canonical signaling pathway in the pioneer growth cones themselves, promoting their motility by suppressing Abl signaling to stimulate filopodial growth while presumably reducing substratum adhesion. This propels the axons as they establish the connection between successive segments.     

Morbidity in acute virus hepatitis B on the territory of Kabardin-Balkaria

Morbidity in acute virus hepatitis B (AVHB) in Kabardin-Balkaria during the period of 1992 to 2003 was analyzed. The dynamics of changes in the age groups of AVHB patients, as well as in the structure of the transmission routes of the disease, was analyzed. The level of AVHB morbidity in the Kabardin-Balkar Republic was lower in recent years than the average level of such morbidity in the whole of Russia. The sharply defined irregularity in the territorial distribution of AVHB cases was established. The highest morbidity rates in AVHB were registered in Nalchik, as well as in Chegem and Prokhladnensk regions. The leading role in the formation of the morbidity in acute virus hepatitis B on the territory of Kabardin-Balkaria belongs to Nalchik, where 56.8% of AVHB cases were registered. In the structure of the transmission routes of AVHB the prevalence of artificial paths was noted; among them, the highest proportion belonged to parenteral medical manipulations in outpatient clinics (32.9%). The proportion of AVHB cases associated with the intravenous use of drugs was 6.9%. In the age structure of AVHB patients adults prevailed, and among them the highest number of cases was registered in the age groups of 20 - 29 years and 30 - 39 years. In 2002 the total proportion of AVHB cases among the patients of these age groups reached 68.3%.