[Gaston Ramon and concise history of anatoxins (to the centenary of discovery)].

The article analyzes past history, main milestones of making, research and improvement of anatoxins from works of Gaston Ramon who first proposed 100 years ago method of obtaining reliable vaccine preparation (anatoxin) on the basis of formalin neutralized diphtheria (and then tetanus) toxin (1922-1923) to nowadays scientific achievements in prevention and treatment of these infectious diseases.

Gaston Ramon (to Centenary of the discovery of anatoxins).

In the history of science, there are great scientists who, without being physicians, wrote golden pages in the History of Medicine. Such was Louis Pasteur, founder of scientific microbiology and immunology. Such was his follower Gaston Ramon (1886-1963), French veterinarian and immunologist who created 100 years ago first anatoxin for active prevention of diphtheria and later tetanus and thus opened era of anatoxins (toxoids) - vaccines based on toxin molecule devoid of toxic properties, but preserving immunogenicity and antigenic specificity. For many centuries, diphtheria (originally known as 'croup') was incurable contagious disease, especially among children. In XIX century, it affected in France up to 30,000 people per year and killed every second infected child. In 1888, at the Pasteur Institute (Paris), Emile Roux (1853-1933) and Alexandre Yersin (1863-1943) demonstrated for first time that symptoms of diphtheria are caused not by bacteria themselves, but by deadly toxin released by them. The long-term search for method of treatment and prevention of diphtheria did not bring the desired result. It will take many years, before Gaston Ramon in 1923 will be able to neutralize diphtheria toxin by acting on it with formalin at certain temperature and thus will receive "anatoxin", mean of vaccination against diphtheria. The article analyzes stages of these studies, which proved high effectiveness of anatoxin and proceeded with widespread implementation of vaccination against diphtheria and later tetanus in short time in France and in Russia (with active participation of Pavel F. Zdrodovsky, 1890-1976). The separate section of the article is devoted to life story of Gaston Ramon and his activities in the Pasteur Institute. The scientist who opened the era of anatoxins did not become Nobel Prize winner, despite the fact that various organizations and scientists from many countries of the world have nominated him 155 times for the Nobel Prize in Physiology or Medicine in different years. He received recognition in France, his Motherland: Gaston Ramon is holder of the Grand Cross of the Order of the Legion of Honor and streets, colleges, lyceums, schools are named after him.

[The Becoming and Development of the Scientific School of Physiology of Kidneys and Water-Salt Metabolism in Novosibirsk].

The article considers analysis of stages of becoming and development of scientific school of physiology of kidneys and water-salt metabolism in at the chair of normal physiology of the Novosibirsk State Medical Institute (University) being one of branches of prominent physiological school of I. P. Pavlov-L. A. Orbeli-A. G. Ginetsinsky and his disciples. An original periodization of its history (precondition, becoming, development and concluding periods) is proposed. The fundamental role of professor A.G. Ginetsinsky in becoming of the given physiological school and its further development under the guidance of professor Ya.D. Finkinshtein are established. The key directions of activities of this scientific school such as links of reflex mechanisms of osmoregulation; the ontogenic features of osmoregulatory mechanisms, role of hypothalamic-pituitary system hormones in maintenance of water-electrolyte homeostasis, osmoregulatory reflexes at various pathophysiological processes, regulation of micro-circulatory processes of formation of cerebro-spinal liquid, development of conceptions of reflex regulation of ionic homeostasis are established and analyzed. The study demonstrated that the given physiological school fully conforms to criteria of scientific school (availability of leader, intergenerational continuity, unity of problematics, duration of existence in time and space, recognition of input into science by disciplinary scientific community).

[Molecular epidemiological analysis of hiv infection in northern seaports of Russia].

The results of the molecular-epidemiological analysis of HIV-1 variants circulating in Arkhangelsk and Murmansk - northern seaports of Russia - were presented. In these seaports the HIV-1 variants belonging to subtype A1 were predominant (93% in Murmansk, 83% in Arkhangelsk). In addition to these variants, viruses of other subtypes such as B, C, D and recombinant forms CRF02_AG and CRF03_AB were identifed. The heterogeneity of circulating HIV-1 variants was higher in Arkhangelsk than in Murmansk. According to the results of phylogenetic analysis, subtype A1 sequences formed the common branch with nucleotide sequences of IDU-A strains found in other regions of Russia. HIV-1 variants of subtype B sub-clustered with sequences of East European B-variants. The recombinant strains CRF02_AG formed the common branch with HIV-1 sequences from Central Asia republics of the former USSR. Among 124 therapy-naive patients from Arkhangelsk and Murmansk (n = 124) the transmitted resistance was less than 5%.

[QUANTITATIVE DNA EVALUATION OF THE HIGH CARCINOGENIC RISK OF HUMAN PAPILLOMA VIRUSES AND HUMAN HERPES VIRUSES IN MALES WITH FERTILITY DISORDERS].

Infertility is an actual medical and social problem. In 50% of couples it is associated with the male factor and in more than 50% of cases the etiology of the infertility remains insufficiently understood. The goal of this work was to study the prevalence and to perform quantitative analysis of the human herpes viruses (HHV) and high carcinogenic risk papilloma viruses (HR HPV) in males with infertility, as well as to assess the impact of these infections on sperm parameters. Ejaculate samples obtained from 196 males fall into 3 groups. Group 1 included men with the infertility of unknown etiology (n = 112); group 2, patients who had female partners with the history of spontaneous abortion (n = 63); group 3 (control), healthy men (n = 21). HHV and HR HPV DNA in the ejaculates were detected in a total of 42/196 (21.4%) males: in 31 and 11 patients in groups 1 and 2, respectively (p > 0.05) and in none of healthy males. HHV were detected in 24/42; HR HPV, in 18/42 males (p > 0.05) without significant difference between the groups. Among HR HPV genotypes of the clade A9 in ejaculate were more frequent (14/18, p = 0.04). Comparative analysis of the sperm parameters showed that in the ejaculates of the infected patients sperm motility as well as the number of morphologically normal cells were significantly reduced compared with the healthy men. The quantification of the viral DNA revealed that in 31% of the male ejaculates the viral load was high: > 3 Ig10/100000 cells. Conclusion. The detection of HHV and HR HPV in the ejaculate is associated with male infertility. Quantification of the viral DNA in the ejaculate is a useful indicator for monitoring viral infections in infertility and for decision to start therapy.

[The federal state educational standard and teaching of history of medicine].

The article considers actual issues of teaching of history of medicine in Russia in connection with transition of higher medical school of Russia to the new Federal state educational standard of high education if the third generation meaning placement of discipline in education process, programs of training, personnel support.

[Interaction of herpesviruses with mature human spermatozoa in the model system in vitro].

The DNA of human herpesviruses (HHV), including the herpes simplex virus (HSV) and cytomegalovirus (CMV), is often identified in ejaculates of patients with urogenital diseases and infertility. At least a part of viral DNA is associated with cell fraction of ejaculate. However, it remains unclear how the semen is infected by the virus. It can be located in gametes or be capable of infecting mature germ cells, including motile sperm cells. In order to resolve this issue, interactions of the CMV and HSV with human sperm cells were studied using an original optimized model of the herpesviral infection of male gametes in vitro. The analysis of the immunofluorescent staining of gametes for viral antigens has shown that CMV infected 2% gametes, while HSV infected 17.26 ± 2.58% gametes. The fraction of progressively motile sperm cells contained 13.99 ± 4.64% infected cells. Localization of HSV was studied by the confocal microscopy. Sometimes, viral gB protein was found on sperm cell membrane. In addition, optical scanning of other cells has shown the intracellular localization of the viral proteins. In the majority of spermatozoa, the viral proteins were observed in the head and neck. In some cells, they were located in the middle piece or, rarely, in the equatorial segment. In general, after in vitro infection HSV antigens were located in the same areas of the sperm cells as in ejaculates from infected patients. According to DNA-DNA hybridization in situ, gametes containing HSV DNA accounted for 16.94 ± 5.28%, which is consistent with the results obtained in the immunofluorescence assay. It can be concluded that mature male gametes are infected by HHV in the genital tract, where the virus binds to the sperm cell membrane and enters the cell. Interaction of HHV with progressively motile sperm cells implies a vertical viral transmission upon fertilization and points to the necessity of testing ejaculate for herpesviruses infections.

[PROBIOTICS, NUTRITIONAL STATUS AND RESISTANCE TO RESPIRATORY INFECTIONS IN INFANTS].

Aim of this study was to investigate the efficacy of prophylactic use of a liquid probiotic form based on Enterococcus faecium L3 in children first year of life to increase resistance to acute respiratory infections (ARI) in the winter-spring period and improve nutritional status. In a specialized (psychoneurologic) orphanage of St. Petersburg within three months of winter-spring period in 2014 observed 29 children in the first year of life. Observed children were randomly divided into two groups. The main group (n = 14) within three months received daily per os liquid probiotic form based on E.faecium L3 in a daily dose of 1.5 x 10(9) CFU. A control group of children (n = 15) was comparable with the main group by gender and age. The children observed groups studied the incidence of ARI; number of vaccinated children; the number of children who received two or more vaccinations at the same time; the number of children with acute infectious diseases within 1 month after vaccination; dynamics of Chulitskaya index, body mass index, body weight and length. The data obtained are subjected to statistical analysis, the results were considered significant at p < 0.05. The results showed that the use of probiotic forms E.faecium L3 in infants helped to reduce the average number of ARI cases per child (0.29 ± 0.13 vs. 0.73 ± 0.12 in the control group; p < 0.05) only in the first month of the observation that combined with a significantly higher BMI values increase this month (0.54 ± 0.25 vs. 0.07 ± 0.22 kg/m2 in the control group; p < 0.05). Use the liquid probiotic form E.faecium L3 in infants had a positive impact on overall health, which is reflected in the implementation of routine vaccination activities--in the main group, the number of children who received two or more vaccinations at the same time was 18.1% more.

[THE BOLOGNA PROCESS AND THE FEDERAL STATE EDUCATIONAL STANDARD OF HIGH EDUCATION].

The article reveals characteristics of entering of high medical school of Russia in the Bologna process. The Russian Federation joined this process in 2003. The features of implementation of the new Federal state educational standard of high education of the third generation in area of training "Health care and medical sciences".

[Evgeniy Mikhaiylovotch Tareyev as founder of Russian nephrology].

The article follows continuity of becoming and development of nephrology in Europe and Russia. The role of Evgeniy Mikhaiylovotch Tareyev (1895-1986) is revealed as a founder of nephrology in second part of XX century. In our country nephrology is considered as an independent scientific discipline. E.M. Tareyev developed prominent scientific clinical school accepted in Russia and abroad.

[The traditional Ayurvedic medicine about pseudo-doctoring as exemplified by "Charaka Samhita"].

The article considers the findings about pseudo-doctoring represented in one of the most ancient medical sources on our planet--treatise "Charaka Samhita" (Carakasamhita). This treatise is the most important text of Ayurveda, a traditional medical system developed in the Hindustan sub-continent during millenniums.

Detection and quantification of human herpes viruses types 4-6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract diseases.

Acute and chronic infections of the seminal tract are among the most common causes of male infertility. As at least half of male infertility cases are classified as idiopathic, some of these cases might be attributed to asymptomatic infection. The detection and quantification of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6) DNA in semen samples were performed. A total of 232 patients were divided into five groups: (i) infertile men with varicocoele; (ii) men with idiopathic infertility; (iii) infertile men with chronic inflammatory urogenital tract diseases (IUTD); (iv) fertile men with IUTD and (v) men whose partners had a history of pregnancy loss. In the study population, the prevalence of viral DNA was 17.7, 3.4% for EBV, 5.2% for CMV, 6.5% for HHV-6, 0.43% for EBV + CMV, 0.87% for EBV + HHV-6 and 1.3% for CMV + HHV-6. The median viral loads for EBV, CMV and HHV-6 were 500, 2250 and 250 copies/mL respectively. Of the sperm cell fractions, derived from infected samples 87.5% contained viral DNA. No association between EBV and fertility disorders or IUTD was found. CMV detection was much higher in the group of patients with infertility and concomitant IUTD compared with the other groups combined (18.5% vs. 5.4%, p = 0.03) and associated with reduced sperm cell count (39.5 × 10(6) /mL vs. 72.5 × 10(6) /mL, p = 0.036). Immunostaining of spermatozoa from infected samples and in vitro-infected cells detected CMV in sperm heads, tails and connecting pieces and revealed attachment to sperm membrane and intracellular localization. HHV-6 was the more common in fertile men with chronic IUTD than in the other groups combined (19% vs. 6.3%, p = 0.018) and had no effect on sperm parameters. The results suggest that both CMV and HHV-6 may contribute to the aetiology of IUTD and, moreover, CMV-associated IUTD can lead to male sterility.

[The gladiators of the Ancient Rome: social status and medical care].

The article considers issues of history of fights of gladiators in relation with life and daily shores of gladiators of the Ancient Rome, their medical care and their status in society and customs.

[The stages of development of Ayurvedic medicine].

The Ayurveda medicine as one the three traditional systems of healing developed during millennia at the Hindustan subcontinent (the ancient India). Nowadays, Ayurveda medicine is widely used in many countries. The present day researchers mark out and analyze several periods in its history.

[The detection of minimal residual disease in patients with chronic B-cell lymphatic leukemia using patient-specified polymerase chain reaction].

The new effective protocols of treatment of chronic B-cell lymphatic leukemia, including purine analogs and monoclonal antibodies, provide robust remissions under this disease. Accordingly, the requirements to remission quality assessment are changed too. In particular the assessment of minimal residual disease is obligatory. To assess minimal residual disease in terms of quantity in case of chronic B-cell lymphatic leukemia the technique of polymerase chain reaction was applied in real time with patient-specific primers from the area of V-D-J combinations of genes of heavy chain of immunoglobulin. The study included samples from 60 patients suffering of chronic B-cell lymphatic leukemia. In 15 of them (25%), it was impossible to apply neither the sequence analysis of genes of heavy chain of immunoglobulin nor the fitting of patient-specific primer. The results of quantitative determination of minimal residual disease were obtained in 45 patients (55 tests). The minimal residual disease was detected in 30 of 55 samples (54.5%) and was not detected in 25 of 55 samples (45.5%). At the same time, the quantitative determination of minimal residual disease was implemented in regard to the initial level of neoplastic cells. The method sensitivity qualified by serial dilutions, consisted 10(-5) or 1 neoplastic cell to 100 000 normal cells. The comparative analysis was applied to the results of determination of minimal residual disease using two methods -polymerase chain reaction in real time using patient-specified primers and four-color flow cytofluometry. The determination of minimal residual disease with both methods was implemented in 37 patients (45 tests). The results of both methods matched in 93.3% (42 tests out of 45) with maximal disparity of one degree. Then Spearman factor consisted 0.87 (p < 0.0001). In 3 out of 45 tests (6.7%) neoplastic cells were detected with only one method. In the first case, it was the method of four-color flow cytofluometry and in other two cases it was polymerase chain reaction in real time. Therefore, the detection of minimal residual disease under chronic B-cell lymphatic leukemia using the method of polymerase chain reaction in real time is rather sensitive and specific and correlates with the results received with the method of four-color flow cytofluometry. The results are the same in the case of using anti-CD20 monoclonal antibodies under treatment.

[The fiftieth anniversary of the Russian Peoples Friendship University (on the history the faculty of medicine)].

The article presents the history of the Russian Peoples Friendship University and of the faculty of medicine in particular from the moment of its organization to nowadays.

[The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men].

The frequency and spectrum of mutations and the IVS8- T polymorphism of the CFTR gene have been studied in a sample of 963 in Russian infertile men. Mutations have been found in 48 out of 1926 analyzed chromosomes (2.5%) in the heterozygous state (n = 46) and in the compound heterozygote L138ins/N1303K (n = 1/n = 1). A CFTR gene mutation was combined with the 5T allele (mutCFTR/5T) in 11 patients. The following mutations have been found: F508del (n = 18), CFTRdele2,3 (21kb) (n = 9), W1282X (n = 7), 2143delT (n = 4), 3849+10kbC>T (n = 2), L138ins (n = 2), 1677delTA (n = 1), 2184insA (n = 1), 3821delT (n = 1), G542X (n = 1), N1303K (n = 1), and R334W (n = 1). The F508del mutation is the most frequent; it has been detected in 37.5% of the affected chromosomes. The total proportion of four mutations (F508del, CFTRdele2,3 (21kb), W1282X, and 2143delT) is about 79% of all mutations found. The 5T allele has been found in 10.9% infertile men and 4.8% of control men. Significant differences in the frequency of the IVS8-5T variant of the CFTR gene have been found between these groups (p = 0.005), as well as between infertile patients without mutations and control men (p = 0.019). In total, the mutations and/or 5T allele have been found in 14.6% of the patients examined. These data indicate increased frequencies of the mutations of the CFTR gene and its allele variant IVS8-5T in Russian infertile men.

[Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more frequently encountered in idiopathic infertility and correlates with the reduction in sperm parameters].

The present investigation was undertaken to study the detection rate of herpes simplex virus (HSV) and cytomegalovirus (CMV) in the ejaculates of males with infertility and to evaluate the impact of virus infection on the major parameters of sperm. Ejaculates from 808 patients were studied. As compared with apparently healthy individuals, the coupled males with primary infertility were found to have HSV more frequently in both the whole ejaculate (31% versus 17%; p = 0.049) and the fraction of actively motile spermatozoa (30% versus 8%; p = 0.016). Ejaculate HSV detection directly correlated with the reduced amount of actively motile spermatozoa (p = 0.0001) and the smaller proportion of morphologically normal forms of germ cells (p = 0.002). CMV was found to have no impact on the motility and morphology of spermatozoids in the ejaculate. Both HSV and CMV in the male ejaculate were significantly more frequently detectable in winter months. The findings lead to the conclusion that HSV is one of the factors for male infertility and can negatively affect the results of assisted reproductive technologies.

[Nikolai Ivanovich Pirogov in British historical and medical literature].

The article gives evidence to the actual conceptions of the British historical medical literature about the input of N. I. Pirogov into world science.