Expression of Aß42, τ-Protein, p16, p53 in Buccal Epithelium: Prospects for Use in the Diagnostics of Alzheimer's Disease and Rate of Aging.

The expression of Aß42, and τ-protein, and p16 and p53 proteins was analyzed in the buccal epithelium of elderly and senile patients with Alzheimer's disease. We revealed enhanced synthesis of Alzheimer's disease markers Aß42 (by 15-30 times) and τ-protein (by 5 times) in comparison with the corresponding values in people without neurodegenerative pathology of the same age groups. In addition, increased synthesis of proteins of cell aging and apoptosis p16 (by 6-10 times) and p53 (by 2-3 times) was observed in patients in comparison with age-matched persons without neuropathology. These data suggest that complex analysis of the expression of Aß42, τ-protein, p16, and p53 in the buccal epithelium is a promising method for in vivo diagnosis of Alzheimer's disease and assessment of the rate of aging during the development of this pathology.

Skin Fibroblasts as the Object for Clinical Diagnosis of Parkinson's Disease in Persons of Different Ages.

We compared the expression of Aß42 peptide, τ-protein, and α-synuclein in the substantia nigra and skin fibroblasts of elderly and senile patients with Parkinson's disease and subjects without neuropathology. Expression of markers in the studied tissues was assessed by immunohistochemical and immunocytochemical methods. The expression of Aß42 peptide, τ-protein, and α-synuclein in the substantia nigra of elderly and senile patients with Parkinson's disease was higher by 11-31 times than in subjects without neuropathology. In skin fibroblasts of patients with Parkinson's disease, the expression of Aß42 peptide and α-synuclein was 3-14 times higher than in subjects without neuropathology, and expression of τ-protein did not significantly differ in the studied groups. Thus, immunocytochemical analysis of the expression Aß42 peptide and α-synuclein in skin fibroblasts can be a simple method of early diagnosis of Parkinson's disease in elderly persons.

[Melatonin as a molecular marker of age-related pathologies].

The review has described melatonin as a prognostic marker of invasive and non-invasive diagnostic of organism aging time and age-related pathology. Decreasing of melatonin level in buccal cells has correlated with patient age. Melatonin level in patients with Alzheimer disease has decreased. Melatonin level in blood plasma has correlated with severity of menopausal syndrome. Melatonin secretion in enterocytes increased during gastric ulcer. In oncology patients was described changes of 6-COMT - metabolite of melatonin in urine in dependent of histology type and stage of disease. Thus, melatonin is the molecular marker, which characterized integral processes in neuro-immuno-endocrine system and can be verified by non-invasive methods in peripheral tissues and biological fluids of organism.

[Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аß42 in CSF in case of AD, but CSF taking may have a number of side effects. Less traumatic taking of sampling tissues for the diagnosis of AD is in use of epithelium biopsy and blood portion. An increase in the expression of the hyper phosphorylated form of τ-protein is shown in blood lymphocytes of AD patients. An increase in the content of high molecular weight forms of phosphorylated t-protein and amyloid precursor protein-APP was also revealed in blood platelets of AD patients. Changes in the amount of 2 miRNA families - miR-132 family and miR-134 family were revealed in blood cells 1-5 years before the manifestation of clinical signs of AD. An increase in the concentration of bound calcium, synthesis of peptides Aß40 and Aß42, τ protein was observed in AD skin fibroblasts. In the olfactory and buccal epithelium an increase in the expression of hyper phosphorylated form of τ-protein and Aß peptide was detected in patients with AD. Verification of AD markers in peripheral tissues for biopsy have the important significant for life diagnostics, prevention and and target AD treatment.

[Palivizumab: four seasons in Russia].

In 2010, the Russian Federation (RF) registered palivizumab--innovative drug, based on monoclonal antibodies for passive immunization of seasonal respiratory syncytial virus (RSV) infection in children of disease severe progress risk group, which include primarily premature infants, children with bronchopulmonary dysplasia and hemodynamically significant congenital heart disease. Currently, palivizumab is included in the list of recommended medicines and medical care standards of different countries, including Russia. In the review the results of Russian research on the progress of RSV infection, its epidemiology and immunization experience gained over the 2010-2014 period are summarized in relation to the foreign data. During the four epidemic seasons palivizumab immunization covered more than 3,200 children of severe RSV infection risk group with a progressive annual increase in the number of patients who received the drug. Geography of palivizumab immunization is also greatly expanded in our country during this time. If during the first two seasons measures of immunization were taken mainly in Moscow and St. Petersburg, at the present time, thirty one territorial entities of the Russian Federation have the experience in the drug application. Analysis of the results of RSV infection immunization (made in several regions) confirms the high clinical efficacy and palivizumab safety already demonstrated in international studies. In addition, the analysis presents the potential to improve the efficiency of the integrated RSV infection immunization programs, realizing in the establishment of high-risk child group register, adequate counseling for parents, as well as the development of the routing of patients and coordination of interaction between different health institutions during the immunization.

[Slow infections of humans and animals].

This review is dedicated to the 60-th anniversary of the exploration of slow infections of humans and animals caused by viruses and prions.

[Identification of microorganisms based on the effect of giant Raman scattering].

AIM: Development and evaluation of express diagnostics of microorganisms for reduction of time spent on study execution. MATERIALS AND METHODS: Giant Raman scattering effect and proposed substrate with metallic nano-balls of silver were used for identification and indication of microorganisms. Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus saprophyticus, Candida albicans, Escherichia coli, Bacillus subtillis, Pseudomonas aeruginosa were used as objects of study. All the microorganisms were cultivated in dense nutrient media and non-fluorescent microbiological membrane filters. RESULTS: Giant Raman scattering method on the substrates used increases sensitivity of indication and specificity of identification of microbes compared with other existing express methods and allows to see the signal from a single bacterium when exposed to laser light. The methodic proposed was also used to determine sensitivity of bacteria to antimicrobial preparations. CONCLUSION: The proposed hardware and method may be used for express diagnostics of processes of microbial nature.

[The painting of A. Laktionov "After the surgery" and destiny of its characters].

The article is devoted to the plot of the painting of Alexander Laktionov (1910-1972) "After the surgery", stored in the Kursk art gallery n.a. A.A. Deineka. The central theme is outstanding surgeon, member of the USSR Academy of Medical Sciences S.S. Yudin has a casual conversation about the team work in N. V. Sklifosovsky First Aid Research Institute with his colleagues D.A. Arapov, A.A .Bocharov and B.S. Rozanov. Each of the painted surgeons made a great contribution to the military medicine. Biographical summaries and medical contribution of these surgeons are described.

[Life extension study on high-yield non-myeloablating bone marrow transplantation from young to old mice].

Tissue renewal is the known phenomenon, when the progeny of resident or circulated stem cells (SC) replaces the vanishing cells. The delivery of stem cells via circulation should result in stem cell homing and differentiation into wide variety of tissues and gives promise as therapy for many diseases of tissue failure including aging itself. To test this hypothesis, we created chimeric mice C57BL/6 by bone marrow (BM) transplantation from young 1.5 months old donors to 21.5-months old recipient mice of the same strain C57BL/6. We applied here the recently published new transplantation technique, which allows to get high scores of chimerism due to very high amount of transplanted cells (1.5 x 10(8) per mouse or 25% of its total BM count). In the earlier works only 1% of total BM count (about 5 x 10(6) cells per mouse) was usually transplanted to lethally irradiated mice, what excluded the possibility to apply this method for life extension. As a result of the modified technique implementation, the mean post-transplantation life (starting the 21.5 months old) of treated mice was 4.9 months versus 3.4 months for untreated mice. The difference in 1.5 months counts for 44% extension of mean post-transplantation life.

[Surgical help organization during wartime].

Immediate proximity of medical groups of special purpose from the troops led to reduction of transportation time. 64% of wounded received medical help during first 2 hours after the incident. All wounded received medical help, even those, who were lethally wounded. 0.6% of wounded finished their treatment on the stage of qualified medical help, 97.3% were evacuated on the next stages and 2.1% had died. 10.2% of patients finished treatment in hospitals of specialized medical stage, 88.2% were sent to next evacuation stages and 1.6% had died. Emergency specialized surgical help was rendered to 43% of wounded. All stages of medical evacuation should be developed in full, in view of the impossibility of further evacuation under certain conditions. At the same time, multiple staging of medical evacuation should be avoided. Evacuation by means of air-transportation should be considered the main way of transportation of the wounded. Medical groups of special purpose are considered to be the leading field medical formations during wartime.

[Prion diseases and the biosecurity problems.]

The review presents the current state of the problem of prions and prion diseases with an emphasis on theepidemiological and epizootological risks of pathogens that cause fatal neurodegenerative diseases in humans and animals. The results of molecular genetic studies of the conversion of normal PrPc prion protein molecules to infectious forms of PrPd, resistance to physical disinfection methods, in particular exceptional thermal stability, and their ability to overcome interspecific barriers, while increasing virulence, are described. The possibility of infection not only by nutrition, when eating even heat-treated meat of sick animals, but also due to surgical interventions, especially neurosurgical and ophthalmic, as well as the use of immunobiological preparations, are emphasized. Since there are currently no means for the effective treatment of prion diseases in the world, attention is drawn to the high degree of relevance for the biosafety of the country to develop domestic highly sensitive test systems that can effectively detect prion infectious protein in vivo at the preclinical stage of the disease. The latest methods of automatic protein amplification and identification of prion proteins are briefly described as the most promising areas of research in the field of diagnosis of prion diseases.

[Chronic persistent infections of anterior segment of eye: clinico-laboratory aspects].

AIM: Improvement of therapy of chronic ophthalmic infectious diseases during assessment of functioning of different arms of immune system. MATERIALS AND METHODS: Three hundred and fifty patients with chronic red-eye syndrome were tested by immunofluorescence assay on the presence of antigens of herpesviruses, adenoviruses and Chlamydia in samples from conjunctiva. Expression of 11 cytokines' genes was measured in peripheral blood mononuclear cells by reverse transcription polymerase chain reaction. Production of IFN-alpha and IFN-gamma, levels of serum and spontaneously produced interferon as well as level of susceptibility to the range of immunomodulating preparations were measured during study of interferon status in whole blood cells. Study of parameters of cytokine, interferon and immune statuses was performed in 70 patients. Counts of T- and B-lymphocytes, T-helpers, NK-cells as well as level of circulating immune complexes were measured during study of immune status. RESULTS: Antigens of herpes simplex virus and adenoviruses were detected in samples from conjunctiva in 27% (95 persons) and 36% (126 persons) of patients respectively. Enhanced level of expression of several cytokines (IL-2, IL-4) in studied patients compared with healthy volunteers was observed. Expression levels of IL-12 and TNF-alpha mRNAs were, in opposite, in 2 - 3 times lower. Disorder of IFN-alpha and IFN-gamma synthesis on post-transciption level was observed in 60 - 90% of patients. Decrease of absolute numbers of total T-lymphocytes and T-helpers as well as increase of absolute number of NK-cells was noted in 20%, 25%, and 27% of patients respectively. CONCLUSION: Assignment of individually oriented antiviral, antibacterial and immunomodulating therapy allowed to mitigate intensity of clinical symptoms in 30 -60% of patients with chronic persistent infections of anterior segment of eye.

[Use of tourniquets in limb combat injuries].

The garrot is one of the most well-known means by stemming of an exterior flow of blood of injured limbs. The article presents analyze of frequency, of indicated values and faults during the using of garrot in modern conditions of the combat in the Northern Caucasus (1994-2002). On the base of 104 wounds of great vessels, the authors make a conclusion about the necessity of using of the garrot only in the cases of absolute indications, when the other method of hemostasia, more simple and secure, is impossible.

[Extraperitoneal complications in gun-shot penetrating wounds of the stomach].

The article after a short literature review presents data of analyze of progression of extra-peritoneal visceral pathology by wounded persons with penetrating wound of stomach. There was described frequency of morbidity of extra-peritoneal organs in dependence on flow of peritonitis. Were marked differences in frequency of progression of peritonitis in conditions of fragment and ballistic wounds. In course of effectuated research was marked dependence between frequency of lethal outcomes and flow of peritonitis and added diseases of respiratory organs, uropoiesis, cardiovascular system. There was effectuated a comparative analysis of frequency of appearance of pathology of marked systems in dependence on localization of ballistic wound. Also there was shortly described a clinical-laboratorial presentation in conditions of appearance of diseases of extra-peritoneal organs.

[Organization of surgical aid for gunshot wounds of the large bowel in the armed conflicts on Northern Caucasus].

The article presents generalization of experience of organization of surgical aid for gunshot wound of large bowel in the armed conflicts on Northern Caucasus. Were studied results of treatment of 272 wounded persons. Were detected 249 wounds of segmented intestine, 23 wounds of straight intestine. 78% of injured had multisystem injuries. All wounded persons had fire peritonitis, which is a logical result penetrating wound of stomach. On the base of results of treatment were proposed algorithms of surgical tactic in condition of wound of large bowel, also were proposed original methods of closing of major softgranulating wounds of perineum. The article presents a generalized experience of work in sphere of treatment of given category of wounds in coloproctologic center CMCH by Vishnevsky A.A.

Efficacy of the synergic action of myoinositol, tyrosine, selenium and chromium in women with PCOS.

OBJECTIVE: The aim of the study is to investigate the efficacy of a treatment with myoinositol plus L-tyrosine, selenium, and chromium in women with polycystic ovarian syndrome (PCOS). PATIENTS AND METHODS: One hundred and eighty-six women, with diagnosis of PCOS, were divided in four groups according to their clinical features. Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology. Phenotype B: androgen excess + ovulatory dysfunction. Phenotype C: androgen excess + polycystic ovarian morphology. Phenotype D: ovulatory dysfunction + polycystic ovarian morphology. All patients were given daily for six months a compound with 2 g myo-inositol, 0.5 mg L-Tyrosine, 0.2 mg folic acid, 55 mcg selenium, 40 mcg chromium. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after. RESULTS: Phenotype A showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased. In the phenotype B, 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported. In the phenotype C, after BMI had followed the treatment for six months, it decreased in a statistically significant manner. In the phenotype D, 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated. CONCLUSIONS: Our study reported how the synergistic action of myoinositol, L-tyrosine, selenium, and chromium could restore normal menstrual cycle, ovulation, and decrease weight in these patients.

[Assessment of the health status and working capacity of electric charge plant operators].

High-power broadband electromagnetic pulses of nanosecond range duration have been found to adversely affect the health status and working capacity of electric charge plant operators. A system of measures to protect the workers from exposure to such pulses, which is based on the hygienic regulation of the exposure, has been implemented.

[Health state and performance of operators in electric discharge facilities--sources of electromagnetic impulses].

The authors revealed that potent broadband electromagnetic impulses in nanosecond range have negative influence on health state and performance of electric discharge facilities operators. Created system of measures protecting workers from such impulses is based on hygienic regulation of the exposure.

Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI.

[Microwaves and blood-brain barrier]. / Mikrovolny i gematoéntsefalicheskii barér.

It is presented the analytical review of the effect of radiofrequency and microwave radiation on function on blood-brain barrier (BBB) in experimental animals. Analysis of referenced papers encompasses the issue of the relation of BBB changes on the power and temporal parameters, regimens of generation of acting radiation and its unevenness. Along with this the authors tried to generalize the cited works considering the marker, used in BBB studies, its molecular mass, to present the sensitivity of isolated brain structures under influence of microwaves to the permeability of several substances, their dependence on thermogeneity of acting levels as well as to draw attention to reversibility of detected changes.