Antibacterial Effect of Thiosulfinates on Multiresistant Strains of Bacteria Isolated from Patients with Cystic Fibrosis.

The multiresistance of A. ruhlandii 155B, B. cenocepacia 122, and P. aeruginosa 48B strains isolated from patients with cystic fibrosis was established. The antibacterial effect of allicin, dimethyl thiosulfinate, and dipropyl thiosulfinate on multidrug-resistant strains was shown. Thiosulfinates can have both bacteriostatic and bactericidal effects depending on the microorganism and the concentration. The studied thiosulfinates may be candidates for the development of alternative antibiotic drugs to treat infections caused by multidrug-resistant pathogens.

Plasma methionine depletion and pharmacokinetic properties in mice of methionine γ-lyase from Citrobacter freundii, Clostridium tetani and Clostridium sporogenes.

PK studies were carried out after a single i.v. administration of 500 and 1000 U/kg by measuring of MGL activity in plasma samples. L-methionine concentration was measured by mass spectrometry. After single i.v. injection of 500U/kg the circulating T1/2 of enzymes in mice varies from 73 to 123min. The AUC0-tinf values determined for MGL 500U/kg from C. freundii, C. tetani and C. sporogenes are 8.21±0.28, 9.04±0.33 and 13.88±0.39U/(ml×h), respectively. Comparison of PK parameters of three MGL sources in the dose of 500U/kg indicated the MGL C. sporogenes to have better PK parameters: clearance 0.83(95%CI: 0.779-0.871) - was lower than C. tetanii 1.27(95%CI: 1.18-1.36) and C. freundii 1.39(95%CI: 1.30-1.49). Mice plasma methionine decreased to undetectable level 10min after MGL 1000 U/kg injection. After MGL C. sporogenes 500U/kg injection plasma methionine level completely omitted after 10min till 6h, assuming the sustainability of negligible levels of methionine (<5µM) in plasma of mice for about 6h. The recovery of methionine concentration showed the advantageous efficiency of MGL from C. sporogenes: 95% 0.010-0.022 vs 0.023-0.061 for MGL C. freundii and 0.036-0.056 for MGL C. tetani. There are no significant differences between methionine cleavage after MGL C. tetani and MGL C. sporogenes i.v. injection at all doses. MGL from C. sporogenes may be considered as promising enzyme for further investigation as potential anticancer agent.

Sulfoxides, Analogues of L-Methionine and L-Cysteine As Pro-Drugs against Gram-Positive and Gram-Negative Bacteria.

The problem of resistance to antibiotics requires the development of new classes of broad-spectrum antimicrobial drugs. The concept of pro-drugs allows researchers to look for new approaches to obtain effective drugs with improved pharmacokinetic and pharmacodynamic properties. Thiosulfinates, formed enzymatically from amino acid sulfoxides upon crushing cells of genus Allium plants, are known as antimicrobial compounds. The instability and high reactivity of thiosulfinates complicate their use as individual antimicrobial compounds. We propose a pharmacologically complementary pair: an amino acid sulfoxide pro-drug and vitamin B6 - dependent methionine γ-lyase, which metabolizes it in the patient's body. The enzyme catalyzes the γ- and ß-elimination reactions of sulfoxides, analogues of L-methionine and L-cysteine, which leads to the formation of thiosulfinates. In the present work, we cloned the enzyme gene from Clostridium sporogenes. Ionic and tautomeric forms of the internal aldimine were determined by lognormal deconvolution of the holoenzyme spectrum and the catalytic parameters of the recombinant enzyme in the γ- and ß-elimination reactions of amino acids, and some sulfoxides of amino acids were obtained. For the first time, the possibility of usage of the enzyme for effective conversion of sulfoxides was established and the antimicrobial activity of thiosulfinates against Gram-negative and Gram-positive bacteria in situ was shown.

[Influence of high concentration of antibodies to NGF during early embryogenesis on formation of mice behavior in postnatal period].

In this work the influence of high concentration of antibodies to NGF on mouse's progeny has been investigated. During immunization with NGF the highest concentrations of antibodies were created in the first and third days of pregnancy (in different groups of animals). The dependence of abnormalities of mice postnatal development on level of antibodies to NGF at different stages of early embryogenesis has been established. Increasing of abnormalities in the formation of early behavioral acts and more clinically apparent anomalies in the somatic maturation in case of maximum of antibodies on day I of pregnancy has been showed. Immune responses to NGF during early embryogenesis of mice cause lag in the formation of behavioral acts. The latter are characterized by difficulties in sensor-motor coordination of the limbs and more clinically apparent in mice with a maximum of antibodies on day 1 of embryonic development. Infantilism in developing of contacts between progeny and mothers detected in mice with immune reactions may be a sign of serious mental dysontogenesis. The accelerated development of working memory established in mice with immune response to NGF requires further study of the development of cognitive abilities in these animals. The obtained results illustrate the important regulatory role of NGF at the early stages of development of the nervous system.

[Development and experience in clinical use of computer monitoring systems in the cardiology intensive care unit]. / Razrabotka i opyt klinicheskoi ékspluatatsii monitorno-komp'iuternoi sistemy otdeleniia neotlozhnoi kardiologii.

To develop national monitor computer systems (MCS) for intensive cardiological care units, which should be reliable, easy-to-use, and cheaper than their foreign analogues is a pressing scientific and practical problem for Russian medical instrument making. The paper presents the results of development of and clinical experience with MCS at the intensive cardiological care unit of the Republican Clinical Cardiology Dispensary in the Republic of Udmurtia (Izhevsk).

[The combined therapy of chronic pyoderma taking into account body immunological reactivity and staphylococcal antibiotic resistance]. / Kompleksnaia terapiia khronicheskoi piodermii s uchetom immunologicheskoi reaktivnosti organizma i antibiotikorezistentnosti stafilokokkov.

Summarizing the results of treatment in 23 patients the authors propose an effective two-staged method to treat chronic pyoderma. This method is based on administration of synthetic peptide of thymus--"thymogen", which is used to correct the immune status and increase sensitivity of staphylococci to antibiotics at the zones of cutaneous affection. The second stage of this method consists in administration of antibiotics in combination with stimulators of phagocytosis and humoral immunity. The results prove the high efficiency of thymogen application in complex management of chronic pyoderma: up to 73.9% of clinic recoveries.

[The provision of dermatovenereological care for the servicemen of the Soviet forces in Afghanistan]. / Okazanie dermatovenerologicheskoi pomoshchi voennosluzhashchim sovetskikh voisk v Afganistane.

The article summarizes the experience of dermovenereological aid to the servicemen, shows the ratio between dermovenereological patients and all the other categories of patients concerning a number of first-complaint visits, hospitalizations and incapacitations. The author gives concrete advice on the improvement of dermovenereological aid.

Correlation between cutaneous sarcoidosis and systemic sarcoidosis.

Twenty patients with cutaneous sarcoidosis and 21 patients carrying isolated skin sarcoids were studied. (We use the term 'sarcoid' to emphasize that exclusively skin was altered.) Both groups were compared by clinical and histological patterns and certain data concerning the state of the mononuclear phagocyte system (MPS). It was found that skin lesions in sarcoids and sarcoidosis do not differ regarding either in clinical or histological manifestations. The changes in the functional activity of monocytes and macrophages were the same. The data obtained allow us to suggest that sarcoids should be regarded as a systemic disease connected with changes in the MPS reaction.

[The immunocorrective therapy of pyoderma caused by staphylococci multiply resistant to antibiotics]. / Immunokorrigiruiushchaia terapiia piodermii, obuslovlennykh stafilokokkami, polirezistentnymi k antibiotikam.

Examinations of 126 patients with staphylococcal pyodermas have helped detect a relationship between the total antibiotic sensitivity of staphylococci isolated from the involved skin and the patient's immunity status. The total antibiotic sensitivity of staphylococci in directly proportional to the blood level of T-lymphocytes, to the degree of their sensitization to staphylococcus in the leukocyte migration inhibition test, and to the value of IgM/IgG ratio. A new synthetic preparation of thymus, thymogen, had a modulating effect on the lymphocytes of pyoderma patients, manifesting by the increment of the total count of T-lymphocytes and T-helpers. A reduction of the total antibiotic resistance of the agent in foci of skin infection and normalization of the immunologic reactivity parameters were recorded in 23 patients with chronic pyodermas after a course of thymogen therapy. An effective method for the management of chronic pyoderma by a combination of thymogen with antibiotics is suggested.

[The ulcerative form of skin sarcoidosis]. / Iazvennaia forma sarkoidoza kozhi.

A female patient suffering from the ulcerative form of skin sarcoidosis is described and the literature dealing with this problem is reviewed. Peculiar features of this case are described: ulceration of the nodes, which is an extremely rare phenomenon; no involvement of other organs, lungs included, was detectable, which is not typical of ulcerative sarcoidosis; small-nodular elements are parallelled by nodes (Boeck's small-nodular sarcoid and Darier-Roussy's subcutaneous sarcoids) in this patient, this evidencing an uniform pathologic process in the skin and subcutaneous fat. Ulceration in this patient is explained by the development of allergic vasculitis of the immediate hypersensitivity type (leukocytoclastic vasculitis and manifest increase of the level of circulating immune complexes). Prednisolone therapy has resulted in an excellent clinical effect.

[Urticarial vasculitis]. / Urtikarnyi vaskulit.

A female patient aged 39 with urticarial vasculitis is described. She has developed stubborn not itching blisters on the skin, suffered from periodic fevers, arthralgias; laboratory analyses have shown leukopenia, hypocomplementemia, immune complexes circulating in the blood and fixed in the skin vessel walls. Histologic examination has revealed leukocytoclastic vasculitis. The differential diagnosis between this condition, chronic urticaria, and lupus erythematosus is discussed.

[Clinical variants of Wegener's granulomatosis]. / K voprosu o klinicheskikh variantakh granulematoza Vegenera.

A female patient is described, suffering from a lingering superficial form of Wegener's granulomatosis. The disease has been diagnosed on the basis of its prolonged (7 yrs) relatively benign course, isolated involvements presenting as skin and nasal mucosa ulcers, hard palate and nasal septum defect, and histologic shifts (necrotizing paling granulomas, combined with vasculitis). Low prednisolone doses have been quite effective in therapy of this condition.

[Cytophotometric and electron microscopic studies of chronic human skin lymphomas. II. Research on lymph node involvement]. / Tsitofotometricheskoe i élektronno-mikroskopicheskoe issledovaniia khronicheski protekaiushchikh limfom kozhi cheloveka. II. Issledovanie porazheniia limfaticheskikh uzlov.

Results of electron microscopic and cytophotometric studies of biopsy material from lymph nodes of patients with cutaneous lymphomas with low degree of malignancy are discussed, with special reference to early diagnostic criteria of the disease. Specific characteristics of tumor tissue involve the presence of atypical lymphocytes with marginal condensed chromatin extrusions of nuclear material, deep invaginations of the nuclear membrane, nuclear pockets, excess of the mean DNA content per nucleus above the diploid standard level, more than 5% of nuclei being in the hyperdiploid area. Electron microscopic and cytophotometric methods allowed to diagnose the tumor injury of lymph nodes, when the traditional histological techniques revealed no signs of malignancy.