The Relationships Among an Activity of the Alternative Pathway Respiratory Flux, a Content of Carbohydrates and a Frost-Resistance of Winter Wheat

A content of carbohydrates and dehydrins in the leaves, activities of the alternative (AP) and the cytochrome (CP) pathways of respiration in mitochondria, isolated from leaves, during cold hardening continuous light (5 °C) and dark conditions with sucrose (2 °C) and relationships among these parameters and a frost-resistance of winter wheat have been investigated. The direct relationship among the content of carbohydrates, the activity of AP and frost-resistance of winter wheat has been detected. It has been concluded that the activity of the alternative oxidase during cold hardening of winter wheat depends on the content of soluble carbohydrates and is necessary to maintain metabolic (red/ox) homeostasis in the cell at low temperatures

PHARMACOECONOMIC ANALYSIS OF TREATMENT OF OUT-OF-HOSPITAL COMPLICATED ABDOMINAL INFECTIONS WITH NEW-GENERATION CARBAPENEM — ERTAPENEM

In a surgeon’s practice, complicated intra-abdominal infections (CII) are one of the most frequent nosological entities. E. Proteus spp., Klebsiella spp. are considered to be leading activators of out-of-hospital CII. For the first time in a Russian economic environment the authors, using mathematical modeling methods, have conducted a clinical and economic research of the new carbapenem, ertapenem, for monotherapy of complicated intra-abdominal infections. They have calculated the total cost, including the cost of CII treatment subject to indicators such as efficiency of treatment and infection-related probability of death (attributive lethality). Results of the «susceptible-infected-susceptible» model were used to assess the impact of acquired bacterial resistance on the efficacy of treating complicated intra-abdominal infections. As a result it was found that in the case of out-of-hospital complicated intraabdominal infections, it is more advisable from the clinical and economic standpoint to start treatment with ertapenem; less advisable is to start with the combination of ceftriaxone and metronidazole or the combination of ciprofloxacin and metronidazole. Key words: clinical and economic analysis, ertapenem, complicated intra-abdominal infections, resistance. (Pediatric Pharmacology. – 2010; 7(1):29-40

PHARMACOECONOMIC ANALYSIS OF TREATMENT OF OUT-OF-HOSPITAL COMPLICATED ABDOMINAL INFECTIONS WITH NEW-GENERATION CARBAPENEM — ERTAPENEM

In a surgeon’s practice, complicated intra-abdominal infections (CII) are one of the most frequent nosological entities. E. Proteus spp., Klebsiella spp. are considered to be leading activators of out-of-hospital CII. For the first time in a Russian economic environment the authors, using mathematical modeling methods, have conducted a clinical and economic research of the new carbapenem, ertapenem, for monotherapy of complicated intra-abdominal infections. They have calculated the total cost, including the cost of CII treatment subject to indicators such as efficiency of treatment and infection-related probability of death (attributive lethality). Results of the «susceptible-infected-susceptible» model were used to assess the impact of acquired bacterial resistance on the efficacy of treating complicated intra-abdominal infections. As a result it was found that in the case of out-of-hospital complicated intraabdominal infections, it is more advisable from the clinical and economic standpoint to start treatment with ertapenem; less advisable is to start with the combination of ceftriaxone and metronidazole or the combination of ciprofloxacin and metronidazole. Key words: clinical and economic analysis, ertapenem, complicated intra-abdominal infections, resistance. (Pediatric Pharmacology. – 2010; 7(1):29-40

ФАРМАКОЭКОНОМИЧЕСКИЙ АНАЛИЗ ЛЕЧЕНИЯ ВНЕБОЛЬНИЧНЫХ ОСЛОЖНЕННЫХ АБДОМИНАЛЬНЫХ ИНФЕКЦИЙ КАРБАПЕНЕМОМ НОВОГО ПОКОЛЕНИЯ — ЭРТАПЕНЕМОМ

In a surgeon’s practice, complicated intra-abdominal infections (CII) are one of the most frequent nosological entities. E. Proteus spp., Klebsiella spp. are considered to be leading activators of out-of-hospital CII. For the first time in a Russian economic environment the authors, using mathematical modeling methods, have conducted a clinical and economic research of the new carbapenem, ertapenem, for monotherapy of complicated intra-abdominal infections. They have calculated the total cost, including the cost of CII treatment subject to indicators such as efficiency of treatment and infection-related probability of death (attributive lethality). Results of the «susceptible-infected-susceptible» model were used to assess the impact of acquired bacterial resistance on the efficacy of treating complicated intra-abdominal infections. As a result it was found that in the case of out-of-hospital complicated intraabdominal infections, it is more advisable from the clinical and economic standpoint to start treatment with ertapenem; less advisable is to start with the combination of ceftriaxone and metronidazole or the combination of ciprofloxacin and metronidazole. Key words: clinical and economic analysis, ertapenem, complicated intra-abdominal infections, resistance. (Pediatric Pharmacology. – 2010; 7(1):29-40)В практике врача хирурга осложненные абдоминальные инфекции (ОАИ) — одни из наиболее часто встречающихся нозологических форм. Ведущими возбудителями внебольничных ОАИ считают E. coli, Proteus spp., Klebsiella spp. Авторами впервые в российских экономических условиях при помощи методов математического моделирования было произведено клинико-экономическое исследование использования нового карбапенема — эртапенема для монотерапии осложненных абдоминальных инфекций. Была рассчитана суммарная стоимость, включающая стоимость лечения ОАИ, с учетом таких показателей, как эффективность лечения и вероятность связанной с инфекциями смертей (атрибутивная летальность). Для оценки влияния приобретенной бактериальной резистентности на эффективность лечения осложненных абдоминальных инфекций были использованы результаты модели «восприимчивый — зараженный — восприимчивый». В результате было показано, что при внебольничных осложненных абдоминальных инфекциях с клинико-экономических позиций целесообразнее начинать лечение с эртапенема; менее целесообразно — с комбинации цефтриаксон + метронидазол или с комбинации ципрофлоксацина и метронидазола.Ключевые слова: клинико-экономический анализ, эртапенем, осложненные абдоминальные инфекции, резистентность. (Педиатрическая фармакология. – 2010; 7(1):29-40

Protective properties of recombinant IgA1 protease from meningococcus

The study of enzymatic and protective properties of recombinant IgA1 protease in active and mutant form has shown that the active form of IgA1 protease exhibited species- and type-specificity for mouse and human immunoglobulins. A mutant form, lacking enzymatic activity, had protective properties against meningococcal infection, induced by meningococcus serogroup A, B and C; it protected mice from lethal infection by live virulent cultures of heterologous serogroups of meningococcus. The results obtained in this study suggest that IgA1 protease may be considered as a perspective preparation at the stages of development of a polyvalent vaccine for protection of human against meningococcal infections of various etiology. © 2013 Pleiades Publishing, Ltd

Anti-biofilm and wound-healing activity of chitosan-immobilized Ficin

© 2020 Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination

Protective properties of recombinant IgA1 protease from meningococcus

The study of enzymatic and protective properties of recombinant IgA1 protease in active and mutant form has shown that the active form of IgA1 protease exhibited species- and type-specificity for mouse and human immunoglobulins. A mutant form, lacking enzymatic activity, had protective properties against meningococcal infection, induced by meningococcus serogroup A, B and C; it protected mice from lethal infection by live virulent cultures of heterologous serogroups of meningococcus. The results obtained in this study suggest that IgA1 protease may be considered as a perspective preparation at the stages of development of a polyvalent vaccine for protection of human against meningococcal infections of various etiology. © 2013 Pleiades Publishing, Ltd

The synthetic fluorinated tetracarboranylchlorin as a versatile antitumor photoradiosensitizer

Tetrapyrrolic macrocycles are suitable for a variety of chemical modifications aimed at new agents for binary antitumor treatment and diagnosis. Previously we have reported that the conjugation of one single carborane cage to the chlorin e6 macrocycle, a modification designed for tumor sensitization in photodynamic (PDT) and boron neutron capture (BNCT) therapies, yielded the derivative with a higher photosensitizing potency in the models of transplanted rodent tumors. This effect was mechanistically linked to the localization of the carboranylchlorin in membrane organelles due to the carborane moiety. Further exploring the potential of modified tetrapyrrolic compounds as photoradiosensitizers we synthesized the chlorin derivative carrying four closo-carborane cages (44 boron atoms) and 16 fluorine atoms at the periphery of the macrocycle (fluorinated tetracarboranylchlorin, compound 1). For comparison of the properties of 1, its fluorine free congener (tetracarboranylchlorin 6) was obtained. The water soluble 1 and 6 accumulated preferentially in cells selected for resistance to chemotherapeutic drugs (multidrug resistance and cisplatin resistance) than in the parental non-selected counterparts. Compounds 1 and 6 showed a negligible dark cytotoxicity. In contrast, a monochromatic light illumination of cells loaded with low micromolar concentrations of 1 or 6 triggered rapid (within minutes) photonecrosis as determined by the entry of propidium iodide or SYTOX dyes into the parental as well as into resistant cells. In vivo 1 or 6 (up to 80 mg/kg i.p.) caused no general toxicity in Balb/c or C57BL6 mice. Illumination with a monochromatic light of B16 melanoma transplants in mice injected with 5 mg/kg 1 or 6 caused a significant shrinkage of tumor foci, with no re-growth in 77.8% animals by day 21 post PDT. BNCT on C6 rat glioma xenografts in Balb/c nu/nu mice injected i.p. with 5 mg/kg 1 led to a decrease of tumor foci and cure of animals by day 29 whereas the radiosensitizing potency of 6 was less pronounced. This difference was attributable to a limited intratumoral accumulation of 6. Altogether, an extensive modification of the chlorin macrocycle periphery with polyfluorines and polycarboranes yielded potent and well tolerable compounds for PDT and BNCT. © 2020 Elsevier Lt