Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver

Several hundred million people are exposed to the risk of leishmaniasis, a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies. In humans, L. tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in the site of the insect bite, but the parasites can also penetrate to internal organs. The relationship between the host genes and development of the disease was demonstrated for numerous infectious diseases. However, the search for susceptibility genes in the human population could be a difficult task. In such cases, animal models may help to discover the role of different genes in interactions between the parasite and the host. Unfortunately, the literature contains only a few publications about the use of animals for L. tropica studies. Here, we report an animal model suitable for genetic, pathological and drug studies in L. tropica infection. We show how the host genotype influences different disease symptoms: skin lesions, parasite dissemination to the lymph nodes, spleen and liver, and increase of levels of chemokines CCL2, CCL3 and CCL5 in serum

Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection

Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. Leishmania major infection in mice is an important model of host–pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens, and a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites’ elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c × CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNγ levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNγ), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype—Lmr21: skin lesions and IFNγ levels, Lmr22: IL-4 levels, Lmr23: IFNγ levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread

Gurdjieff’s anthropology: the concept of conscious human evolution

The main purpose of the article is the disclosure of the ideas of Gurdzhiyev’s anthropological doctrine in which the possibility of spiritual transformation of the person and his conscious evolution are emphasized. The author claims that in the conditions of dissociation of approaches and positions in the anthropological thought there is a need of appeal to the anthroposophic systems designed to fill onesidedness of such directions as psychoanalysis (in many respects absolutizing a role of unconscious processes), the behaviorism (concentrating on behavioral aspect of human existence), the existentialism (emphasizing hopelessness “abandonment of life in the world”). According to the author one of such systems is Gurdzhiyev’s system of conscious evolution of the person, the so-called “The Fourth Way” which is eligible for the status of the translater of the experience of Gnostic tradition in the 20th century

Psychology of the exoteric: on the specifics of spiritual work at the initial stage of mastering esoteric knowledge and experience

The key ideas of esotericism regarding the spiritual transformation of a person in this article are considered in the context of psychological inner work on oneself at the initial (exoteric) stage of mastering esoteric knowledge and experience. It is noted that the external world penetrates into the inner world of a person, "imprinted", becoming an internal reality. This reality has various characteristics, acquires the psychological status of positive and negative emotions. In this regard, esoteric work as a whole is a "guide" for orientation in the space of the inner world and recommendations for changing internal states

Myší model leishmaniózy a jeho využití pro vývoj léků a zkoumání vztahů parazitu a hostitele

Leishmania spp. have a great clinical significance, being a causative agent of leishmaniasis. Leishmania is transmitted to its vertebrate hosts by phlebotomine sand flies. In vertebrates, the parasites infect professional phagocytes (neutrophils, monocytes and macrophages) and a variety of other cells. Clinical symptoms of leishmaniasis range from lesions, local or disseminated, to mucosal and visceral pathology. Twelve million people are infected with Leishmania and 350 million people are under risk of infection in 88 countries. Yet, no vaccine has been developed and the treatment needs significant improvement. In this regard, animal models of leishmaniasis play a key role in understanding the mechanisms of the disease and in finding ways to treat and prevent it. This thesis summarizes the results of my Ph.D. project devoted to refinement of procedures relevant to Leishmania studies and to the use of the optimized protocols for gene mapping and search for antileishmanial drugs. Large-scale cultivation of infective Leishmania parasites is important in a wide range of experimental setups. We adapted a biphasic SNB-9 medium for the large-scale cultivation of Leishmania and compared it with a common liquid medium. We also modified and optimised detection and quantification of Leishmania with PCR-ELISA by using...Původce leishmaniózy Leishmania spp. má velký klinický význam. Leishmania je přenášena na obratlovce flebotomy, drobným dvoukřídlým hmyzem z čeledi Phlebotominae. Parazit infikuje profesionální fagocyty (neutrofily, monocyty a makrofágy) a řadu dalších buněk. Klinické příznaky leishmaniózy se pohybují od vytvoření kožní leze, která může být lokální nebo difuzní, přes mukosní až k viscerální patologii. Prvokem Leishmania je nakaženo dvanáct milionů lidí a 350 milionů lidí v 88 zemích je infekcí ohroženo. Zatím nebyla vyvinuta žádná účinná vakcína a také léčba vyžaduje značné zlepšení. Z tohoto důvodu hrají zvířecí modely leishmaniózy klíčovou roli v pochopení mechanismu onemocnění a v hledání způsobů, jak tuto chorobu léčit a najít účinnou prevenci. Tato práce shrnuje výsledky mého postgraduálního studia věnovaného zdokonalování laboratorního modelu leishmaniózy a jeho využití pro mapování genů a pro zkoumání látky s leishmanicidním potenciálem. Namnožení velkého množství infekčních forem leishmanií je klíčové v mnoha experimentálních postupech. Vypracovali jsme proto postup s dvoufázovým médiem SNB-9 pro pěstování leishmanií ve velkém množství a porovnali tento postup s pěstováním v běžném tekutém médiu. Pro detekci a kvantifikaci leishmanií jsme modifikovali a optimalizovali metodu PCR-ELISA s využitím...Department of Immunology and Clinical Biochemistry 3FM CUÚstav imunologie a klinické biochemie 3. LF3. lékařská fakultaThird Faculty of Medicin

Experimental murine leishmaniasis and its application for drug discovery and study of host-pathogen interactions

Leishmania spp. have a great clinical significance, being a causative agent of leishmaniasis. Leishmania is transmitted to its vertebrate hosts by phlebotomine sand flies. In vertebrates, the parasites infect professional phagocytes (neutrophils, monocytes and macrophages) and a variety of other cells. Clinical symptoms of leishmaniasis range from lesions, local or disseminated, to mucosal and visceral pathology. Twelve million people are infected with Leishmania and 350 million people are under risk of infection in 88 countries. Yet, no vaccine has been developed and the treatment needs significant improvement. In this regard, animal models of leishmaniasis play a key role in understanding the mechanisms of the disease and in finding ways to treat and prevent it. This thesis summarizes the results of my Ph.D. project devoted to refinement of procedures relevant to Leishmania studies and to the use of the optimized protocols for gene mapping and search for antileishmanial drugs. Large-scale cultivation of infective Leishmania parasites is important in a wide range of experimental setups. We adapted a biphasic SNB-9 medium for the large-scale cultivation of Leishmania and compared it with a common liquid medium. We also modified and optimised detection and quantification of Leishmania with PCR-ELISA by using..

Description of mystic experience in Russian religious philosophy of the 19

The article presents the factors influencing the description of mystic experience in the works of Russian religious philosophers of the 19th-20th centuries: V.S. Solovyev, P.A. Florenskiy, S.N. Bulgakov, N.O. Losskiy, I.A. Ilyin, S.L. Frank, V.V. Zenkovskiy. The authors cite several western and contemporary domestic scholars, who research different aspects of mystic experience. Analysis and generalization of works of Russian religious thinkers allows the authors to identify the peculiar features of mystic experience in Russian religious philosophy of the 19th-20th centuries and list its objects. The article gives examples of acquiring mystic experience described in the works of Russian religious philosophers of XIX-XX centuries. The authors come to a conclusion that doctrine of deification or theosis is recognized in Russian religious philosophy of the 19th-20th centuries as the main mystic teaching of Eastern Christianity. General ideas of deification peculiar to Russian religious thinkers are also stated and conditions necessary to acquire this mystic experience are named in the article

The Current State of Religious Education in Russia by the Example of Comprehensive Schools and Higher Educational Institutions of Rostov-on-Don

In the article there is a judgment of the current state of religious education in Russia by the example of comprehensive schools and higher education institutions of Rostov-on-Don. The authors mark a number of problems preventing high-quality improvement of religious education in the Russian Federation and also speak about the achievements in this sphere made lately. In the article the need of improvement of quality of religious education in Russia contacts a huge number of destructive information in the Internet space and its adverse effect on the modern Russian youth and also the substitution of real life by virtual reality and the related with them falling of the intellectual level of development of the young generation which has received the manifestation in ignorance of history and culture of their own country. The authors argue about the changes of the meaning of the category “value” in the modern Russian society. They compare modern understanding of “value” with understanding of “value” of the beginning of the 20th century. A set of traditional cultural values is given in the article, it is necessary to impart these values to the young generation to protect it from the adverse effect of the Internet space and to develop the critical relation to the obtained information

The influence of macroeconomic factors to the dynamics of stock exchange in the republic of Kazakhstan

This article describes the influence of macroeconomic factors on Kazakhstan Stock Exchange Market by using data from 2005 to 2014. Engle-Granger cointegration test has shown that stock index is cointegrated with the exchange rate, interest rate, CPI and oil price. Vector error correction model has confirmed that macroeconomic variables and the stock index has a long-term equilibrium relationship. Moreover, empirical results have shown that stock index can be used as a leading indicator of the economic situation in Kazakhstan. Therefore, the authors decided to consider the impact of major macroeconomic indicators to the dynamics of the stock market of the Republic of Kazakhstan. The Engle-Granger cointegration test results show that the following variables such as exchange rate, 10-years long-term bond rate, the consumer price index and the Brent oil price are cointegrated with stock index, which means that there is a long-term relationship between this stock market index and these variables. With the help of econometric models, the authors have found the factors such as the exchange rate, the 10-year long-term bonds rate, the consumer price index and the Brent oil price (these factors have the long-term relationship with stock market index). Changes in the dynamics of the stock market index in Kazakhstan are caused by changes in the dynamics of Central bank's reserves and export. The analysis has shown that the economy of the Republic of Kazakhstan (the index reflects the situation in the real sector of the economy) remains dependent on world oil prices, the volume of exports and the rate of the national currenc

Modern possibilities of phytotherapy for male infertility from the standpoint of evidence-based medicine

Introduction: Male infertility is an topical medical and social problem of modern reproductive medicine. Its pharmacotherapy is often empirical in nature, and the most popular method remains the use of various herbal substances (phytotherapy), the effectiveness of which remains still understudied in the framework of evidence-based medicine. Materials and Methods: The results of research, thematic, systematic and Cochrane reviews and meta-analyses were searched in Medline/PubMed medical databases over the past 5 years using the search queries "plants male infertility", "plants sperm", "phytotherapy male infertility", "phytomedicinal therapeutics male infertility", "systematic review", "meta-analysis", and "review". Results: The vast majority of herbal substances offered for the treatment of male infertility demonstrate insufficient or contradictory evidence base for their clinical effectiveness, although some of them can be very useful pharmacotherapeutic options in the combined therapy of male infertility. Conclusion: Not all plant substances with a "reproductive effect" positioned in them actually have proven reproductive effects in studies in humans, therefore, the choice of phytotherapeutic agents in the treatment of idiopathic male infertility should be currently approached extremely carefully, especially in cases when we choose phytotherapy as an option for empirical monotherapy of male reproductive disorders