Effects of ACTH6-9-Pro-Gly-Pro Peptide on the Levels of Pro- and Anti-Inflammatory Cytokines in Wistar Rats under Conditions of Chronic Restraint Stress.

We evaluated the effect of ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide on the serum levels of pro- and anti-inflammatory cytokines in experimental animals under conditions of chronic restraint stress. Stress exposure over 2 weeks led to an increase in the levels of IL-1ß, IL-6, and IFNγ in rats. Daily intraperitoneal injection of ACTH6-9-PGP in a dose of 5 µg/kg before stress exposure significantly decreased the levels of IL-6 and IFNγ by 4.8 and 49.3% respectively. Administration of the peptide in a dose of 50 µg/kg decreased the levels of IL-1ß and IFNγ by 51.2 and 39.7%, respectively. However, no changes in the cytokine levels were observed after injection of the peptide in a dose of 500 µg/kg. Thus, ACTH6-9-PGP administered in doses of 5 and 50 µg/kg prevented the stress-induced changes in the levels of pro- and inflammatory cytokines.

Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH(4-7)-PGP (Semax).

We studied the effect of intraperitoneal administration ACTH(4-7)-PGP in doses of 5, 50, 150, and 450 µg/kg to Wistar male rats 12-15 min before modeling restraint stress on the morphofunctional state of the colon. In rats exposed to restraint stress, signs of atrophy and inflammatory reaction in the colon wall, changes in functional activity and number of mast cells, and increased serum level of corticosterone were observed. Administration of the peptide led to a decrease in corticosterone concentration, alleviated stress-induced pathomorphological changes, and promoted adaptation of the intestinal wall to stress. The positive effects of ACTH(4-7)-PGP can be determined by multifunctional nature of the physiological and pharmacological effects of the neuropeptide.

Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress.

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 µg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 µg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.

Morphological Changes in the Large Intestine of Rats Subjected to Chronic Restraint Stress and Treated with Selank.

We studied the effects of Selank on the condition of the colon wall in Wistar male rats subjected to restraint stress. Selank was injected intraperitoneally in doses of 80, 250, and 750 µg/kg 15 min before stress exposure. In rats subjected to stress, signs of atrophy, inflammatory reaction, and changes in the number and functional activity of mast cells were observed against the background of increased corticosterone level. Selank administration led to a decrease in corticosterone levels, reduced pathomorphological manifestations of stress exposure, and accelerated adaptation. These effects were presumably realized due to multifunctional biological effects of Selank.

State of Colon Microbiota in Rats during Chronic Restraint Stress and Selank Treatment.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 µg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with Fungicide Activity of Biogenic Peptide Cecropin P1.

Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide cecropin P1 (CecP1) have been reported. Now we report biological testing K. pinnata extracts containing CecP1 as a candidate drug for treatment of wounds infected with Candida albicans. The drug constitutes the whole juice from K. pinnata leaves (not ethanol extract) sterilized with nanofiltration. A microbicide activity of CecP1 against an animal fungal pathogen in vivo was demonstrated for the first time. However, a favorable therapeutic effect of the transgenic K. pinnata extract was attributed to a synergism between the fungicide activity of CecP1 and wound healing (antiscar), revascularizing, and immunomodulating effect of natural biologically active components of K. pinnata. A commercial fungicide preparation clotrimazole eliminated C. albicans cells within infected wounds in rats with efficiency comparable to CecP1-enriched K. pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not exhibit neither wound healing activity nor remodeling of the scar matrix. Taken together, our results allow assumption that CecP1-enriched K. pinnata extracts should be considered as a candidate drug for treatment of dermatomycoses, wounds infected with fungi, and bedsores.

Bactericide, Immunomodulating, and Wound Healing Properties of Transgenic Kalanchoe pinnata Synergize with Antimicrobial Peptide Cecropin P1 In Vivo.

Procedure of manufacturing K. pinnata water extracts containing cecropin P1 (CecP1) from the formerly described transgenic plants is established. It included incubation of leaves at +4°C for 7 days, mechanical homogenization of leaves using water as extraction solvent, and heating at +70°C for inactivating plant enzymes. Yield of CecP1 (after heating and sterilizing filtration) was 0.3% of total protein in the extract. The water extract of K. pinnata + CecP1 exhibits favorable effect on healing of wounds infected with S. aureus (equal to Cefazolin) and with a combination of S. aureus with P. aeruginosa (better than Cefazolin). Wild-type K. pinnata extract exhibited evident microbicide activity against S. aureus with P. aeruginosa but it was substantially strengthened in K. pinnata + CecP1 extract. K. pinnata extracts (both wild-type and transgenic) did not exhibit general toxicity and accelerated wound recovery. Due to immunomodulating activity, wild-type K. pinnata extract accelerated granulation of the wound bed and marginal epithelialization even better than K. pinnata + CecP1 extract. Immunomodulating and microbicide activity of K. pinnata synergizes with microbicide activity of CecP1 accelerating elimination of bacteria.

[Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery]. / Tranzitornoe uvelichenie ob''ema kist kraniofaringiom posle stereotaksicheskoi luchevoi terapii i radiokhirurgii.

Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. MATERIAL AND METHODS: In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. RESULTS: Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). CONCLUSION: Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).

[A giant hyperostotic parasagittal meningioma in a child with neurofibromatosis type II (a case report and literature review)]. / Gigantskaya giperostoticheskaya parasagittal'naya meningioma u rebenka s neirofibromatozom II tipa (sluchai iz praktiki i obzor literatury).

Large parasagittal meningiomas, in particular hyperostotic ones, in children are rare and problematic in the differential diagnosis. The literature reports only single clinical cases related to this issue; opinions about the indications, surgical treatment options, and prognosis are contradictory. This paper presents a clinical case of a hyperostotic parasagittal meningioma with intra-extracranial growth in a 10-year-old boy with neurofibromatosis type II significantly worsening the prognosis. We discuss the epidemiological and clinical features of childhood meningiomas and issues of their diagnosis, treatment, and prognosis.

[EFFECT OF POLYCOMPONENT PROBIOTICS ON THE COMPOSITION OF COLON MICROBIOCENOSIS DURING EXPERIMENTAL DYSBIOSIS].

AIM: Study the effect of RioFlora Immuno Neo and Bifiform probiotics on the colon microflora composition under the conditions of experimental dysbiosis in mice. MATERIALS AND METHODS: Medicinal dysbiosis was modelled in animals by gentamicin administration, probiotics were administered intragastrally by the end of dysbiosis formation. Quantitative and qualitative study of mucous microflora of mice colon was carried out by a bacteriological method. RESULTS: Correction of dysbiosis by probiotics has resulted in correction of the intestine microflora composition, and more pronounced when RioFlora Immuno Neo was used. CONCLUSION. The results of the study allow to recommend the use of these preparations for selective correction of colon dysbiosis.

[CHANGES IN COLON MICROBIOCENOSIS COMPOSITION AND ANTIOXIDANT PROPERTIES OF COLONOCYTES UNDER THE CONDITION OF EXPERIMENTAL DYSBIOSIS AND EMOXIPIN PROPHYLAXIS].

AIM: Study the composition of colon microbiocenosis and antioxidant properties of colonocytes under the conditions of experimental dysbiosis and prophylaxis application of emoxipin. MATERIALS AND METHODS: With the aim of prophylaxis, antioxidant emoxipin was administered to mice, in which medicinal dysbiosis was formed by intraperitoneal administration of gentamicin. Quantitative and qualitative study of mucous microflora of the mice colon was carried out by a bacteriological method. The state of lipid peroxidation system was judged by the content of acylhydroperoxides and malonic dialdehyde, system of antioxidant protection--by enzyme activity (catalase and superoxide dismutase). RESULTS: Experimental dysbiosis of the colon manifested by changes in the composition of mucous microflora of the animals and antioxidant properties of colonocytes. Dysbiosis prophylaxis by emoxipin resulted in normalization of the activity of antioxidant protection enzymes and products of lipid peroxidation in intestine tissue. CONCLUSION: The study results allow to consider, that use of emoxipin results in an increase of adaptive-compensatory capabilities of the macroorganism during experimental dysbiosis.

[The role of biofilms in pathogenesis of chronic bacterial rhinosinusitis].

The objective of the present work was to study the contribution of biofilms to the development of chronic bacterial rhinosinusitis. A total of 50 patients with this pathology were available for the examination. Mucosal swabs were taken from the middle nasal passages of all the patients to be used for the detection of biofilms by luminescence microscopy. The lactoferrine content in mucosal secretion from the nasal cavity was determined by an immunoenzymatic assay. Two groups of the patients presenting with bacterial rhinosinusitis were distinguished in the study of impression smears from nasal cavity mucosa by luminescence microscopy; one of them was comprised of biofilm-positive patients the other of biofilm-negative ones (56% and 44% respectively). The patients showing biofilms over nasal cavity mucosa had the lactoferrine content in mucosal secretion on the order of 0.0033±0.0008 mg/l compared with 0.0068±0.00075 mg/l in the biofilm-negative patients and 0.55±0.0005 mg/l in the healthy volunteers (controls). In other words, the biofilm-positive patients presenting with chronic bacterial rhinosinusitis had two times lower content of lactoferrine in mucosal secretion from the middle nasal passages than those in the biofilm negative group and 126 times lower content of lactoferrine than in the control group.

[Characteristics of medulloblastoma in children under age of three years].

We present a series of 51 medulloblastoma in children under three years, collected in N.N. Burdenko Neurosurgical Institute from 2000 to 2010. 57% of the tumors showed desmoplastic/nodular histology. Performed fluorescence in situ hybridization (FISH) analysis revealed the MYC oncogene amplification in 4%, the MYCN oncogene amplification - in 8%, isochromosome 17q - in 16% of cases. 9q deletion was found in 8% of desmoplastic/ nodular medulloblastomas. Our results showed that desmoplastic/nodular medulloblastoma has a positive predictive value for progression-free survival. Another feature of a biology of medulloblastomas in children younger than three years is the lack of nuclear accumulation of beta-catenin, and 6q deletion. Medulloblastomas with MYCN oncogene amplification often exhibit desmoplastic/nodular histology and a relatively favorable outcome. The most unfavorable prognostic marker is the MYC oncogene amplification, which in our series of 100% combined with the large cell/anaplastic medulloblastoma and isochromosome 17q - such tumors should be included in the "high risk" protocol.

[Study of the state of parietal microflora and wall of the large intestine of mice under the influence of anomalous magnetic field].

AIM: Study the possible qualitative and quantitative changes of microbial community of the parietal mucin of the large intestine and the state of the wall of the large intestine in experimental animals underbackground and anomalous influence of geomagnetic field. MATERIALS AND METHODS: CBA mice were put under the influence of anomalous magnetic field comparable to its intensity in Zheleznogorsk (3 Oe) for 1 and 2 weeks. Quantitative and qualitative study of mucous microflora of the large intestine of the mice was performed by bacteriological method. Identification of the microorganisms was performed by microbiological analyzer "Multiskan-Ascent" and commercial test-systems "Lachema-Czech Republic": ENTHEROtest-16, STAPHYtest-16, Streptotest-16, En-COCCUStest-16; for lactobacilli and bifidobacteria identification - API 50 CHL (bioMerieux). Bacteria content in 1 g of material was calculated by the number of microorganism colonies grown. RESULTS: A pattern of changes of mucous microflora of the intestine and the state of the wall of the large intestine of the experimental animals that had been put under the influence of anomalous magnetic field is shown. During evaluation of qualitative and quantitative diversity of microbial community of parietal mucin of the large intestine of the mice under the influence of magnetic field on the background and anomalous levels changes not only in quantity and frequency of detection of obligate, transitory flora but also cell elements of mucous membrane of the wall of the large intestine were established. CONCLUSION: The results of the study allow to make a conclusion about the presence of reactivity of the parietal microflora of the intestine of the mice to the influence of the anomalous magnetic field. This leads to changes in cell elements in the mucous membrane of the wall that manifest by infiltration of the connective tissue stroma by leucocytes and reconstruction of epithelium, that are features of dysbiosis.

[The risk for recurrent pulmonary tuberculosis in dispensary registration group III patients].

A statistical method was used to specify the significance of the most commonly encountered risk factors for recurrent pulmonary tuberculosis. Among others, 10 factors that substantially influenced the development of an early recurrence were identified. These are distributed as follows: medical factors, such as comorbidity, the undulating course of a tuberculous process, a contact with a tuberculosis patient, an ineffective basic course of therapy for the underlying disease, intercurrent diseases, a decay phase, major and minor residual changes. Social risk factors were fewer; however, they also had a great influence--the unemployed and prisoners. A combination of 4 significant signs or more was of significance to the development of an early recurrence; in case of more than 2 risk factors, the likelihood of a recurrence proved to be insignificant (p < 0.05).

[Impact of introduction of the WHO tuberculosis-controlling recommendations adapted to the Russian conditions on the Russian statistical tuberculosis data]. / Vliianie vnedreniia adaptirovannykh k Rossiiskim usloviiam rekomendatsii voz po bor'be s tuberkulezom na otechestvennye statisticheskie pokazateli po tuberkulezu.

The authors share their experience in introducing the WHO tuberculosis-controlling recommendations adapted to the Russian conditions into the Republic of Mariy El, in the Ivanovo, Oryol, and Tomsk Regions. All the areas are marked by high rates of diagnosis of MBT in the clinical diagnostic laboratories of the general medical network, by the increased rates of detection of patients of tuberculosis who isolate Mycobacterium tuberculosis, by the enhanced efficiency of treatment of patients with tuberculosis, as shown by the Russian statistical data, by the lower rates of growth of the contingents of patients with tuberculosis or by their reduction.