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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 58, No 7-8 (2013)
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ORIGINAL PAPERS

3-11 378
Abstract
On the base of previously developed microbial models high effective scheme for screening of inhibitors of sterol biosynthesis (ISB) is proposed. It is based on cultivation of halophilic bacteria Halobacterium salinarum (former Halobacterium halobium), possessing mevalonate pathway of sterol biosynthesis, and cultivation of fungus Acremonium fusidioides (former Fusidium coccineum), that is producer of steroid antibiotic fusidin (fusidic acid), which biosynthesis has great similarity (with coincidence of its initial steps till squalene formation) to cholesterol biosynthesis in human organism. In H.salinarum model ISB are revealed as compounds that inhibit test-culture growth, whereas in A.fusidioides test-system they are revealed as compounds that strongly reduce fusidin production without any visible influence on producer's growth. Mevalonate that is one of the crucial intermediates of sterol biosynthesis remove inhibition induced by many microbial metabolites that is the evidence of their action at early stages of sterol biosynthetic pathway, including HMG-CoA reductase step. Both test-systems are developed as micromethod and could be easily mechanized due to miniaturization of microbiological procedures, cultivation in sterile 96-well plates and usage of automatic micropipettes and dispensers. Effectiveness of both test-systems, as well as their sensitiveness, laboriousness and ability to give false-positive or false-negative results in ISB screening work is compared. The proposed scheme of screening of ISB includes microbial models at early steps of screening procedures and Hep G2 test-system at the late step. The preliminary screening of microbial metabolites possessing antifungal activity at initial step is compulsory. Miniaturization and mechanization of microbial processes and purification of producers' culture broth with micro- and ultrafiltration are under consideration as well.

GUIDELINES FOR PRACTITIONERS

12-16 871
Abstract
Polyorgan insufficiency (POI) Is the main cause of death in ISU patients. The highest rates of morbidity and mortality due to POI are recorded among newborns. Antibbacterial therapy of probable infections processes is widely used in neonatology, however longterm antibacterial therapy is not favouable for newborn infants. The aim of the present study was to investigate the peculiarities of antibacterial therapy in newborn with POI. The trial enrolled 453 infants antibacterial therapy was used in all of them (100%). The most frequent drugs used in the treatment were the III and IV generation cephalosporines and aminoglycosides. The POI antibacterial therapy in severe cases was more intensive and prolonged. The most long-term therapy was applied to newborns weighting 1500 g. Recovery of the organ function served as a criterion for discontinuation of the antibacterial therapy. Antibacterial of neonate infants with POI requires optimization.
17-22 755
Abstract
The data on the efficacy of cycloferon as an agents of antirelapsing therapy in management of 123 patients with chronic hyperplastic sinusitis are presented. The drug induction of endogenous interferons was validated by the properties of the local mucosal immunity, virus invasion and virus persistence in the nasal and accessory nasal sinuses mucosa, as well as by different levels of the interferon production deficiency. The clinical efficacy was stated in 53% of the cases. The relapses were recorded in 13.1% of the patients treated with cycloferon vs. 33.3% of the patients under the local corticosteroid therapy.
23-29 359
Abstract
Thirty four patients with mucormycosis in 10 hospitals of St. Petersburg were observed in 2004-2013. The most frequent underlying diseases of mucormycosis were acute leukoses (64%). In 100% of the patients mucormycosis developed as a nosocomial infection. The risk factors, etiology, basic clinical signs and strategy in the treatment of mucormycosis were analyzed.
30-33 458
Abstract
The problems of prophylaxis of infectious complications in the treatment of oral local mucinous carcinoma are considered relevant to 204 respective cases. More favourable results of the combined and complex treatment of the patients were shown when a multidisciplinary approach was used with obligatory participation of stomatologists. Special stomatologic prophylactic and therapeutic procedures with using reamberin orally and intravenously in the chemo- and radiotherapy and adequate antibiotic therapy during the surgical operation resulted in less frequent infectious complications, that was in favour of the patients life quality. Intraosteal administration of antibiotics was shown preferable.

DRUGS SAFETY

34-39 367
Abstract
Tricyclic antidepressants, not influencing the P450 3A4 activity, are safe in combination with drugs of other groups used in the treatment of comorbid patients. Azaphen is is one of the agents most widely used in the clinical practice. The in vitro electrochemical analysis showed that pipofezin (azaphen) was not a substrate, inductor, and/or inhibitor of cytochrome P450 CYP3A4 isoenzymes. The Guzar programme computer modelling and the literature data demonstrated the substrate affinity of pipifezin to CYP1A2.

REVIEWS

40-47 326
Abstract
The aim of the review was systematization of the data on discordance in expression of estrogen receptors between primary and metastatic breast cancer, different metastases and repeated analyses of the same tissue. The possible reasons for the phenomenon are discussed. The authors emphasize the need to analyze estrogen receptors in breast cancer metastases, regardless of the receptor status of the primary tumor, for predicting the course of the metastatic disease and providing an adequate treatment of the metastatic tumor in strict accordance with its receptor status during drug therapy. The works cited in the search engine Pub Med to May 2013 were analyzed.
48-61 519
Abstract
Physico-chemical and biological properties of sepsis-associated low molecular aromatic compounds are summarized and analysed in the review. Phenylcarbonic acids (PCAs), such as para-hydroxyphenyllactic acid (p-HPLA), phenyllactic acid (PLA), para-hydroxyphenylacetic (p-HPAA), phenylacetic acid (PAA), benzoic acid (BA), and phenylpropionic acid (PPA) are shown to have biorequlatory activity and be able to affect both bacteria and eukaryotic cells. In the review there are presented data on the diagnostic and pathogenetic value of PCAs, their bacteriostatic and bacteriocidal properties and biosynthesis by clinically significant bacterial species, as well as description of the mechanisms of microbial resistance to PCAs, the pathways of PCAs metabolism by prokaryotes, PCAs membrane transport and excretion pathways in humans, the data on the use of PCAs in clinical practice. The authors are of the opinion that PCAs of microbial origin share the metabolic and signal pathways in integration of the microbiome and man. On the basis of the literature data and personal studies the authors validated the hypothesis of possible development of new therapeutic strategies, grounded on regulation of the local and systemic balance of aromatic microbial metabolites in the human body.


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ISSN 0235-2990 (Print)