Prophylactic efficacy of Triazavirin against experimental Forest-Spring encephalitis was studied on albino mice. vs. the active drug Ribavirin. A significant increase of the animal lifespan in the test groups (from 4 to 5 days) and a statistically (p < or = 0.05) valid decrease of the virus accumulation level in the target organ (the brain) were observed.
The efficacy of Triazavirin against the tick-borne encephalitis virus was estimated in the sensitive cell culture vs. the active drug Ribavirin. In a concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the SKEV cell culture.
Rational position of voriconazole in the treatment of oncologic inpatients was shown and the criteria of its use in the algorithms of the therapy and prophylaxis of nosocomial fungal infections were developed. The clinical trial enrolled 50 patients with oncologic pathologies. The patients were divided into two groups of possible invasive candidiasis risk. The patients of one group were treated with fluconazole (Diflucan) and those of the other group were treated with voriconazole (Vifend). The spectrum of the hospital fungal flora was determined and susceptibility of 310 clinically important opportunistic fungi was investigated. All the isolates of Candida albicans and C.tropicalis were susceptible to amphotericin B, fluconazole and voriconazole and 79 and 50% of the isolates were susceptible to intraconazole respectively. As for the C.krusei isolates, 67% was susceptible to amphotericin B, 50% was susceptible to fluconazole, 100% was susceptible to voriconazole and none of the strains was susceptible to intraconazole. By the clinical efficacy voriconazole was superior to fluconazole and comparable with amphotericin B, while superior to it by the number of the side effects and by the cost of the treatment course. It was concluded that voriconazole should be considered as the main agent in the antifungal therapy of oncologic patients.
The hepatoprotective activity of remaxol, reamberin and ademethionine was studied on a model of the liver injury induced by antituberculosis drugs. The study included 30 male uninbred albino rats. The following antituberculosis drugs were used: isoniazid (50 mg/kg) subcutaneously + rifampicin (250 mg/kg) intragastrically + pyrazinamide (45 mg/kg) intragastically (by the procedure of Yu. I. Slivka, 1989). Remaxol, reamberin and ademethionine were administered 1.5 hour prior to the antituberculosis drugs. The treatment course was 14 days. It was shown that remaxol, reamberin and ademethionin were able to correct the structural and functional disorders in the liver due to the use of the antituberculosis drugs. By the impact on the biochemical indices, evident of the liver function condition, remaxol showed the maximum effect. The effect of ream-berin was somewhat lower and the results of the ademethionine use were less significant. Remaxol had also a distinct effect as for lowering the level of the structural injuries in the liver, evident from recovery of the organ histoarchitectonics, less extended carbohydrate, albuminous and fatty degeneration, more active intracellular regeneration. It was noted that ademethionine had an insignificant effect on necrobiosis. Moreover, there was once detected a large necrosis focus, evident of possible stimulation of the liver tissue alteration by the drug.
The effect of betulin derivatives on persistence properties of microorganisms was studied in vitro. It was shown that the antipersistence action of the betulin derivatives depended on their structure and the microbial species. The experimental data on the structure - function relation could be useful in development and synthesis of new agents for therapy of chronic infections associated with persistence of bacterial pathogens in macroorganism.
Analysis of the antibioticograms of the Vibrio cholerae non-01/non-0139 strains showed that in the cultures isolated in the Rostov Region in 1968--1975 there were present markers of resistance to ampicillin (7%), kanamycin (15.8%), rifampicin (3.5%) and trimetoprim/sulfamethoxazole (14%). Among the strains isolated in the Ukraine in 1975 14% was resistant to ampicillin. More than a half of the strains isolated in Uzbekistan in 1990 and 2000-2001, in the Arkhangelsk Region in 1999-2000 and in the Kalmykia in 1999-2005 was antibiotic resistant. In the above regions the strains were resistant to ampicillin (12.5-44.4%), kanamycin (11-55%), rifampicin (1.9-12.5%) and trimetoprim/sulfamethoxazole (25-62.5%). Among the cultures isolated in Uzbekistan in 1990 and 2000-2001 25 and 7.8% were resistant to furazolidone and 31.25% was resistant to streptomycin (1990). All the cultures isolated in the Rostov Region in 2005-2009 were resistant to ampicillin, 50% was resistant to ceftazidim, 57% was resistant to streptomycin and furazolidone, 7.2% was resistant to kanamycin and 14% was resistant to trimetoprim/sulfamethoxazole. The studies revealed an increase of the extent of the V.cholerae non-01/non-0139 resistance spectrum within 1968-2009, simultaneous presence of up to 5 diverse resistance markers and a variety of their combinations, that requires the use of antibacterials for the treatment of the diseases due to the vibrios in strict compliance with the pathogen antibioticogram and their early replace by more efficient drugs.
Antimicrobial activity of bacteriocin S760 (enterocin) produced by Enterococcusfaecium strain LWP760 was studied. Bacteriocin S760 is a cationic, hydrophobic, and heat stable peptide with the molecular weight of 5.5 kDa and pl of 9.8. Enterocin S760 is shown to inhibit in vitro the growth both of sensitive and resistant to antibacterials gramnegative and grampositive bacteria of 25 species. MICs of the bacteriocin S760 vary between 0.05-1.6 mg/l for Escherichia coli 0157:H117, Salmonella typhimurium, Salmonella enteritidis, Campylobacter jejuni, Yersinia enterocolitica, Yersinia pseudotuberculosis, Listeria monocytogenes and Clostridium perfringens, that are main food-borne pathogens, and from 0.4-1.6 mg/l for Streptococcus pyogenes, Streptococcus pneumoniae and Corynebacterium diphteriae. It is also active against antibioticresistant strains of Staphylococcus aureus, Enterobacter cloacae, Acinetobacter baumannii (with MICs of 0.05-3 mg/l), Klebsiella pneumoniae (with MICs of 6 mg/l), Pseudomonas aeruginosa (with MICs of 0.4-25 mg/1), as well against fungi belonging to species of Candida albicans, Candida krusei and Aspergillus niger (with MICs of 0.1-0.2 mg/l). Enterocin S760 is a novel antimicrobial agents useful in medicine, veterinary and food industry.
Verapamyl substance and market verapamyl were investigated with circular dichroism. It was shown that circular dichroism provided rapid and highly efficient determination of the optic isomers and could be recommended as a method for control of drug quality.
Ingavirin was shown to be efficient in inhibition of the pandemic influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v. as well as the influenza virus strain A/Aichi/2/68 (H3N2) in the lungs of the infected mice. After oral administration of Ingavirin the titers of the influenza virus strains in the lung homogenates lowered.
The authors' findings and literature data on the pharmacotherapeut efficacy of cycloferon, an interferon inductor (immunomodulators) are described. The drug effect in the treatment of various socially significant children' diseases, including acute respiratory tract viral infection, bronchial asthma, allergic conditions with infection protection disturbances, mycoplasmic infection, bronchopulmonary complications of acute respiratory tract viral infection with low intensity of free radical oxidation is indicated. The use of cycloferon at the background of vaccination was shown to provide inhibition of the autoimmune processes causing postvaccinal complications in frequently ill children. The results of the use of cycloferon in the treatment of gastrointestinal tract and intestinal infections of both the viral and bacterial genesis are discussed. Cycferon is recommended to be used for correction of the intestine dysbiosis (the microflora level came to normal in 95% of the children). The use of the drug in surgical pathology and in particular in appendicular peritonitis for decreasing the postoperative complications and correction of the immune disturbances due to chronic viral hepatitis C and B in children under the complex therapy is described. The cycloferon safety and efficacy were confirmed by the postmarketing randomized trials.
The study showed that bla(CTX-M) genes were present in the genomes of 71% of cephalosporin resistant Enterobacteriaceae nosocomial isolates (n=833) collected in Russian hospitals within 2003-2007, including 91% of E.coli, 90% of Klebsiella spp., 38% of Enterobacter spp., 31% of Citrobacter spp. (n=9), and 36% of the other Enterobacteriaceae species. The genes belonging to the following subtypes (clusters) were identified: bla(CTX-M-1) (529 bla(CTX-M-15) genes; 25 bla(CTX-M-3) genes; 1 bla(CTX-M-22) gene, 1 bla(CTX-M-23) gene, and 1 bla(CTX-M-34) gene); bla(CTX-M-2) (1 bla(CTX-M-2) gene, and 4 bla(CTX-M-5) genes), and bla(CTX-M-9) (2 bla(CTX-M-9) genes, and 28 bla(CTX-M-14) genes). It was shown that bla(CTX-M) genes were located on high-molecular weight (60-160 bp) conjugative plasmids belonging mainly to the incompatibility groups IncF, IncL/M and IncA/C (bla(CTX-M-15) gene); IncL/M(bla(CTX-M-3) gene); and IncF, IncL/Mand IncI1-ly (CTX-M-14 gene). The gene environments of bla(CTX-M) genes were shown specific for the subtype of the genes. A mobile genetic element ISEcp1 (in some cases deleted or inserted by IS26, IS1, IS10, resTn2, or resTn3 sequences, in direct or reverse position) were detected upstream of bla(CTX-M-3), bla(CTX-M-14), and bla(CTX-M-15) genes. A special characteristic was the sequence between ISEcp1 and bla(CTX-M) gene: 48 bp for bla(CTX-M-15) (except 1 E.coli isolate having such a sequence deleted by 3 bp); 127 bp for bla(CTX-M-3); 42 bp for bla(CTX-M-14). Downstream of bla(CTX-M) and bla(CTX-M-15) genes in the major bacterial isolates orf477 mucA and Delta orf477-Delta mucA sequences were detected respectively. Two isolates had additional Delta orf3 insertion inside of Delta orf477-Delta mucA sequence. Insertion sequence IS903 (intact or deleted) was detected downstream of bla(CTX-M-14) gene. Unlike the others, bla(CTX-M-2) and bla(CTX-M-9) genes were located inside of ISCR1 mobile element, downstream of class 1 integron and orf513 sequence.
The efficacy of levofloxacin and moxyfloxacin vs. the previously tested fluoroquinolones was studied on albino mice with experimental plague due to the Nal(r) mutants of Yersinia pestis 231 and 231 FI-. The plague microbe mutants resistant to nalidixic acid (Nal(r)) generated at a frequency of 10(-10)-10(-9). The resistance to nalidixic acid was not accompanied by the strains loss of the virulence. The Nal(r) mutants were cross resistant to fluoroquinolones (ciprofloxacin, moxyfloxacin). The LD50 for the nontreated animals did not differ from that for the mice treated with nalidixic acid and the fluoroquinolones (when the animals were infected with Nal(r) mutants). The results showed that the criteria of the plague microbe susceptibility/resistance to fluoroquinolones should be revised.
High in vitro and in vivo efficacy of Ingavirin against the Mexican pandemic influenza virus A/H1N1/2009, strains A/California/04/2009 (H1N1) and A/California/07/2009 (H1N1) vs. the reference drug Arbidol was studied and verified when used therapeutically and prophylactically.
Development of secondary immune dysbalance in patients with polytrauma complicated by urinary tract infection (acute pyelonephritis) was observed. In such cases bacterial complications were highly possible, that required the use of immunotropic drugs (cycloferon) increasing the host nonspecific resistance, responsible for Th1 immune response. The cycloferon therapy of the patients with chronic pyelonephritis normalized the lymphocyte electrophoretic mobility promoting efficient recovery of the immune homeostasis. Cycloferon was shown to be effective in the prophylaxis and therapy of infective inflammation in the patients with polytrauma, that was evident of the antibacterial therapy efficacy increasing and more rapid healing of the infective inflammation.
The best therapeutic effect in the treatment of patients with chronic hepatitis B was observed with the use of cycloferon in the scheme of the antiviral therapy. The combination of cycloferon with lamivudine provided complete stable remission in 54.1% of the patients, whereas the use of a-interferon in combination with cycloferon provided remission in 44.1% of the lamivudine-resistant patients. The use of cycloferon in the therapy of chronic hepatitis B made it possible to lower the frequency and manifestation level of the side effects and prevented the lamivudine resistance development and generation of the virus mutants.
The effect of L-lysine-alpha-oxidase from a representative of the Trichoderma genus on the humoral immune response to protein antigens was studied. It was shown that repeated fife-fold intravenous administrations of L-lysine-alpha-oxidase in a dose of 35 U/kg had no depressive action on the humoral immunity. The enzyme had no suppressive effect on the delayed type hypersensitivity to xenogenous erythrocytes. The use of L-lysine-alpha-oxidase in a therapeutic dose or in a twice as higher dose had no reliable effect on the leukocyte migration capacity vs. the control.
It was shown that colloidal silver solution prepared in cooperation with the A. F. Ioffe Physical Technical Institute of the Russian Academy of Sciences, had significant bactericidal activity. Stable bactericidal effect on gramnegative microorganisms was observed after their 2-hour exposition in the solution of colloidal silver at a concentration of 10 ppm. Grampositive capsule-forming microorganisms were less susceptible to the colloidal silver solution: their death was observed after the 4-hour exposition in the solution.
Antiviral properties of Ingavirin were investigated in the Hep-2 cell culture with respect to the human respiratory tract virus (type 5 adenovirus). In concentrations of Ingavirin of 1000, 100 and 10 mcg/ml the generated posterity showed lower infective capacity (by 250, 100 and 10 times respectively). The electron microscopy of the infected cells confirmed the Ingavirin ability to disturb the adenovirus normal morphogenesis.
The use of macrolides in the treatment of chlamydial infection during pregnancy and breast feeding is reviewed from the viewpoint of evidence-based medicine. The clinical experience and research data suggest azithromycin to be safe and effective in the obstetric practice.
