ВЛИЯНИЕ ТИМИЧЕСКИХ ПЕПТИДОВ НА АНАЛЬГЕЗИЮ, ВЫЗВАННУЮ ОСТРОЙ И ПОДОСТРОЙ ИММОБИЛИЗАЦИЕЙ

Objective: Our aim was to investigate the influence of thymic polypeptides on pain sensitivity and to analyze a possible role of the opioid system in the implementation of the analgesia caused by immobilization stress. Methods: The study was performed on male Wistar rats at the Moscow state University named after M. V. Lomonosov. We studied effects of thymus peptides: thymuline (0.15 mg/kg), fraction 5 thymosin (0.25 microgram/kg) and tactivin (0.5 mg/kg) on pain sensitivity in rats using test «tail flick» without stress, with acute (3 h) and sub acute (12 h) immobilization stress. The comparison groups were animals treated with saline and spleen polypeptides. Results: It is shown that preparations of thymus increase the threshold of pain sensitivity in the intact animals. Immobilization stress duration 3 and 12 h in thymus peptides treated rats caused a less pronounced increase in pain threshold than in the control groups (immobilization stress 3 h: tactivin — р=0.025, thymuline — р=0.022, fraction 5 thymosin — р=0.033; immobilization stress 12 h: tactivin — р=0.034, thymuline — р=0.027, fraction 5 thymosin — р=0.036.). The opioid receptor blocker naloxone (1 mg/kg) did not completely block the stress-induced analgesia, indicating the presence of both opioid and non-opioid components in this state. In thymus peptides treated rats, opioid component was less pronounced than in the control groups (tactivin — р=0.031, thymuline — р=0.026, fraction 5 thymosin — р=0.029). Conclusion: Pre-activation of the opioid system by the thymus polypeptides leads to an increase in the share of non-opioid component of the stress-induced analgesia and prevents the depletion of the opioid system in immobilization stress. Цель исследования: исследовать влияние полипептидов тимуса на болевую чувствительность и определить роль опиоидной системы в реализации анальгезии, вызванной иммобилизационным стрессом. Методы: исследование выполнено на самцах крыс линии Wistar в Московском государственном университете им. М.В. Ломоносова. Изучено влияние пептидов тимуса: тимулина (0,15 мг/кг), фракции 5 тимозина (0,25 мкг/кг) и тактивина (0,5 мг/кг) на болевую чувствительность крыс с помощью теста отдергивания хвоста без стресса, при остром (3 ч) и подостром (12 ч) иммобилизационном стрессе. В контрольные группы были включены животные, получавшие физиологический раствор и полипептиды селезенки. По окончании тестирования снижали активность опиоидной системы налоксоном. Результаты: показано, что препараты тимуса увеличивают порог болевой чувствительности у интактных животных. Иммобилизационный стресс продолжительностью 3 и 12 ч на фоне пептидов тимуса вызывал менее выраженное увеличение порога болевой чувствительности, чем в контрольных группах (иммобилизация 3 ч: тактивин — р =0,025, тимулин — р =0,022, фракция 5 тимозина — р =0,033; иммобилизация 12 ч: тактивин — р =0,034, тимулин — р =0,027, фракция 5 тимозина — р =0,036). Блокатор опиоидных рецепторов налоксон (1 мг/кг) не полностью блокировал стресс-вызванную анальгезию, что свидетельствовало о наличии как опиоидного, так и неопиодного компонентов данного состояния. На фоне пептидов тимуса опиоидный компонент был менее выражен, чем в контрольных группах (тактивин — р =0,031, тимулин — р =0,026, фракция 5 тимозина — р =0,029). Заключение: предварительная активация опиоидной системы полипептидами тимуса приводит к увеличению доли неопиоидного компонента анальгезии при стрессировании и препятствует истощению опиоидной системы при иммобилизационном стрессе.

Нейропептиды, цитокины и тимические пептиды как эффекторы взаимодействия тимуса и нейроэндокринной системы

The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The presence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymus peptides and/or cytokines, controlled by them, enter the brain and exert influence on neuronal function, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.В обзоре приведены данные о взаимодействии нейроэндокринной системы и тимуса, осуществляемом через нейроэндокринно-иммунные адаптивные системы организма. Присутствие адренергических и пептидергических нервов в тимусе создает условия для воздействия продуцируемых ими нейропептидов. Последние активируют рецепторы на тимических клетках, влияя на основные процессы в тимусе, включая созревание Т лимфоцитов, продукцию цитокинов, гормонов и пептидов. В свою очередь, продуцируемые тимусом пептиды и/или контролируемые ими цитокины проникают в мозг, влияя на функции нейронов, что создает основу для поведенческих изменений и поддержания гомеостаза в ответ на инфекцию. При старении организма, а также ряде заболеваний — инфекционных, аутоиммунных, нейродегенеративных, онкологических — показаны нарушения взаимодействий процессов в тимусе и центральной нервной системе. Механизмы сигнальных реакций, определяющих эти взаимодействия, еще не ясны, и их понимание будет способствовать развитию комплексных эффективных терапевтических стратегий

ВЛИЯНИЕ ИММУНОАКТИВНЫХ ПРЕПАРАТОВ НА ФОРМИРОВАНИЕ УСЛОВНОГО РЕФЛЕКСА ПАССИВНОГО ИЗБЕГАНИЯ

Aim: The objective of this project was to explore the influence of immunoactive drugs (tactivin, thymulin, and thymosin fraction 5) on the development of the passive avoidance conditioned reflex. Materials and methods: Two types of passive avoidance boxes were used — a regular two-chamber box and a modified three-chamber box, comprising a dark chamber in which rats were exposed to electrical shock, a safe dark chamber, and a light chamber in the center. Results: The project has established that the memory trace persists longer under the influence of the immunoactive drugs in both models, which is consistent with the reference nootropic piracetam test results. Notably, the immunoactive drugs' mnemotropic effect was more pronounced in the modified three-chamber box than in the standard two-chamber box. Using the modified box helped to establish the influence of tactivin, thymulin, and thymosin fraction 5 on the spatial memory component. Immunotropic preparations from thymus caused the animals to select the safe chamber 24 hours later and in subsequent tests. Conclusion: The project’s results indicate that the drugs tested do possess mnemotropic properties, so their range of clinical use can be broadened.Цель исследования: изучить влияние иммуноактивных препаратов (экстракта тимуса, тимулина и 5-й фракции тимозина) на формирование условного рефлекса пассивного избегания. Материалы и методы: в работе использовали установки для формирования условного рефлекса пассивного избегания — классическую двухкамерную и модифицированную трехкамерную, состоящую из темного отсека, где животное получало удар током, темного безопасного отсека и центрального светлого отсека. Результаты: в настоящей работе установлено более длительное сохранение памятного следа на фоне влияния иммуноактивных препаратов в обеих моделях, что сопоставимо с результатами эталонного применения ноотропного препарата пирацетама. Следует отметить, что по сравнению с классической моделью в модифицированной установке заметнее выражен мнемотропный эффект иммуноактивных препаратов. Использование модифицированной установки позволило установить влияние экстракта тимуса, тимулина и 5-й фракции тимозина на пространственный компонент памяти. Иммунотропные препараты тимуса привели к предпочтению заходов в безопасный отсек как через 24 ч, так и при последующих тестированиях. Выводы: полученные в настоящей работе данные указывают на наличие мнемотропных свойств у исследуемых препаратов, что в свою очередь позволяет расширить их спектр клинического применения

Community-acquired pneumonia in adult HIV-infected patients: Course, treatment, and prevention

This is a review of published data on community-acquired pneumonia (CAP) in adult HIV-infected patients. Morbidity of bacterial pneumonia in HIV-infected patients is 5-to 10-fold higher than that in general population. Wide use of antiretroviral therapy (ARVT) is associated with a reduction in mor-bidity of CAP in HIV-infected patients, but this reduction is not as significant as for other opportunistic infections. The most important risk factors for CAP are drug abuse, tobacco smoking, HIV-associated immunosuppression, hepatic cirrhosis, not to be treated with ARVT or ARVT withdrawal. Severe, complicated and invasive course of CAP and poor outcomes are seen more often in HIV-infected patients compared to general population. Bacterial pneumonia should be differed from pneumonia caused by Pneumocystis and from tuberculosis, especially in endemic countries and in patients with insidious onset of the disease. The standard therapy of CAP is applied in all patients independently of HIV status. However, administration of fluoroquinolones is restricted in regions with high prevalence of multi-drug resistant tuberculosis in HIV-infected patients before tuberculosis is excluded. Several studies have demonstrated that, in case of false initial diagnosis, 10-day monotherapy with a fluoroquinolone could form the resistance of Mycobacteria tuberculosis against this drug; this significantly complicates further treatment of tuberculosis and increases the treatment cost. Beta-lactams are not effective against tuberculosis; in 2016, WHO excluded macrolides from the list of medications for therapy of tuberculosis due to their low activity against M. tuberculosis. Therefore, empirical therapy of CAP in HIV infected patients should be started with combination of beta-lactam antibiotic and modern macro-lide. A strong protective effect of PPV23 vaccine against CAP was confirmed in HIV-infected patients, but the highest protective efficacy was seen in patients with relatively preserved immunity compared to patients with CD4 < 200 cells × μL-1

Impact of etiotropic therapy on the immune status of patients with HIV infection and tuberculosis

Aim. To evaluate the impact of etiotropic therapy on the immunological efficiency of treatment in patients with HIV infection in relation to the presence of active tuberculosis (TB) and the baseline count of CD4+ lymphocytes. Subjects and methods. A total of 239 HIV-infected patients were examined and divided into 3 groups: 1) 103 HIV-infected patients with TB who received both anti-TB therapy (ATBT) and antiretroviral therapy (ART); 2) 46 HIV-infected patients with TB who did not receive ART during TB treatment; 3) 90 HIV-infected patients without TB who used ART for the first time. CD4+ lymphocyte counts were measured by flow cytofluorometry in all the patients before and 4 and 12 weeks after treatment. Results. Analysis of an increment in CD4+ lymphocyte counts in the HIV-infected patients with tuberculosis showed that those who had very low baseline CD4+ lymphocyte counts (median, 78 cells/μl) were noted to have significant positive changes (median, +146 cells/ μl) at 12 weeks of ART. Even without ART, effective ATBT in the patients with a well preserved immune system (>350 CD4+ cells/μl) in turn resulted in a substantial increase in CD4+ lymphocyte counts (median, +187 cells/μl following 12-week ATBT). At the same time, 10.9% of the patients showed a decrease in the baseline CD4+ lymphocyte counts during progression or delay in the tuberculosis process, which required that ART should be promptly performed. Conclusion. The investigation of the time course of changes in the increment of CD4+ lymphocyte counts revealed a swifter response to ART as their rapid increment in patients with coinfection (HIV infection concurrent with TB) than that in those with HIV monoinfection. When the baseline CD4+ lymphocyte counts are over 350 cells/μl, the start of ART should be delayed until TB treatment is completed

Features of the course and effectiveness of treatment of tuberculosis in pregnant women with different HIV status

The study presents the results of comparing the social status and the efficiency of TB treatment in pregnant women with or without HIV treated in Krasnoyarsk Regional TB Clinic No 1 in the years 2010-2014. It is based on a retrospective analysis of health cards of 133 pregnant TB patients divided into groups: Group 1 (TB), n=109; Group 2 (TB and HIV), n=24. More than a half of the women (51,3% and 54,1% accordingly) were new TB patients, the others had been previously treated for TB. A moderate immunodeficiency was more often detected in co-infected pregnant women (mean CD4+ lymphocyte count being 387 cells/ml), although in 4 patients the CD4 count was lower than 200 cells/ml. The registered rates of bacterioexcretion and lung disintegration were practically the same (57,7% and 58,3% versus 53,2% and 54,1% accordingly); MDR TB was diagnosed in 51,1% in Group 1 and in 60,0% in Group 2. Results: Patients of both groups had various social problems. However, the most aggravating medico-social factor among the co-infected women was active drug abuse during pregnancy (proved in 37,5%). The clinical course of TB in patients with HIV was severer, they more often developed acute forms of the disease. Preterm delivery was more frequent in TB/HIV cases (46,1% vs. 12,3%, p<0,01). Children born by the women with HIV co-infection showed signs of prematurity and intrauterine growth retardation more often than those born by HIV-negative patients (50,0% vs. 12,3%, p<0,01). Treatment efficiency for TB was authentically less in co-infected cases (33,4% vs. 58,7%, p<0,01). TB recurrence was more often registered in HIV-positive patients (25,0% vs. 3,1%, p<0,01). As for chemotherapy tolerance, treatment adherence or lethality rate, no authentic differences between the groups have been revealed

Impact of etiotropic therapy on the immune status of patients with HIV infection and tuberculosis

Aim. To evaluate the impact of etiotropic therapy on the immunological efficiency of treatment in patients with HIV infection in relation to the presence of active tuberculosis (TB) and the baseline count of CD4+ lymphocytes. Subjects and methods. A total of 239 HIV-infected patients were examined and divided into 3 groups: 1) 103 HIV-infected patients with TB who received both anti-TB therapy (ATBT) and antiretroviral therapy (ART); 2) 46 HIV-infected patients with TB who did not receive ART during TB treatment; 3) 90 HIV-infected patients without TB who used ART for the first time. CD4+ lymphocyte counts were measured by flow cytofluorometry in all the patients before and 4 and 12 weeks after treatment. Results. Analysis of an increment in CD4+ lymphocyte counts in the HIV-infected patients with tuberculosis showed that those who had very low baseline CD4+ lymphocyte counts (median, 78 cells/μl) were noted to have significant positive changes (median, +146 cells/ μl) at 12 weeks of ART. Even without ART, effective ATBT in the patients with a well preserved immune system (>350 CD4+ cells/μl) in turn resulted in a substantial increase in CD4+ lymphocyte counts (median, +187 cells/μl following 12-week ATBT). At the same time, 10.9% of the patients showed a decrease in the baseline CD4+ lymphocyte counts during progression or delay in the tuberculosis process, which required that ART should be promptly performed. Conclusion. The investigation of the time course of changes in the increment of CD4+ lymphocyte counts revealed a swifter response to ART as their rapid increment in patients with coinfection (HIV infection concurrent with TB) than that in those with HIV monoinfection. When the baseline CD4+ lymphocyte counts are over 350 cells/μl, the start of ART should be delayed until TB treatment is completed

Features of the course and effectiveness of treatment of tuberculosis in pregnant women with different HIV status

The study presents the results of comparing the social status and the efficiency of TB treatment in pregnant women with or without HIV treated in Krasnoyarsk Regional TB Clinic No 1 in the years 2010-2014. It is based on a retrospective analysis of health cards of 133 pregnant TB patients divided into groups: Group 1 (TB), n=109; Group 2 (TB and HIV), n=24. More than a half of the women (51,3% and 54,1% accordingly) were new TB patients, the others had been previously treated for TB. A moderate immunodeficiency was more often detected in co-infected pregnant women (mean CD4+ lymphocyte count being 387 cells/ml), although in 4 patients the CD4 count was lower than 200 cells/ml. The registered rates of bacterioexcretion and lung disintegration were practically the same (57,7% and 58,3% versus 53,2% and 54,1% accordingly); MDR TB was diagnosed in 51,1% in Group 1 and in 60,0% in Group 2. Results: Patients of both groups had various social problems. However, the most aggravating medico-social factor among the co-infected women was active drug abuse during pregnancy (proved in 37,5%). The clinical course of TB in patients with HIV was severer, they more often developed acute forms of the disease. Preterm delivery was more frequent in TB/HIV cases (46,1% vs. 12,3%, p<0,01). Children born by the women with HIV co-infection showed signs of prematurity and intrauterine growth retardation more often than those born by HIV-negative patients (50,0% vs. 12,3%, p<0,01). Treatment efficiency for TB was authentically less in co-infected cases (33,4% vs. 58,7%, p<0,01). TB recurrence was more often registered in HIV-positive patients (25,0% vs. 3,1%, p<0,01). As for chemotherapy tolerance, treatment adherence or lethality rate, no authentic differences between the groups have been revealed

Community-acquired pneumonia in adult HIV-infected patients: Course, treatment, and prevention

This is a review of published data on community-acquired pneumonia (CAP) in adult HIV-infected patients. Morbidity of bacterial pneumonia in HIV-infected patients is 5-to 10-fold higher than that in general population. Wide use of antiretroviral therapy (ARVT) is associated with a reduction in mor-bidity of CAP in HIV-infected patients, but this reduction is not as significant as for other opportunistic infections. The most important risk factors for CAP are drug abuse, tobacco smoking, HIV-associated immunosuppression, hepatic cirrhosis, not to be treated with ARVT or ARVT withdrawal. Severe, complicated and invasive course of CAP and poor outcomes are seen more often in HIV-infected patients compared to general population. Bacterial pneumonia should be differed from pneumonia caused by Pneumocystis and from tuberculosis, especially in endemic countries and in patients with insidious onset of the disease. The standard therapy of CAP is applied in all patients independently of HIV status. However, administration of fluoroquinolones is restricted in regions with high prevalence of multi-drug resistant tuberculosis in HIV-infected patients before tuberculosis is excluded. Several studies have demonstrated that, in case of false initial diagnosis, 10-day monotherapy with a fluoroquinolone could form the resistance of Mycobacteria tuberculosis against this drug; this significantly complicates further treatment of tuberculosis and increases the treatment cost. Beta-lactams are not effective against tuberculosis; in 2016, WHO excluded macrolides from the list of medications for therapy of tuberculosis due to their low activity against M. tuberculosis. Therefore, empirical therapy of CAP in HIV infected patients should be started with combination of beta-lactam antibiotic and modern macro-lide. A strong protective effect of PPV23 vaccine against CAP was confirmed in HIV-infected patients, but the highest protective efficacy was seen in patients with relatively preserved immunity compared to patients with CD4 &lt; 200 cells × μL-1

A case of tuberculosis in HIV-infected pregnant women

Here is presented the clinical surveillance of course coinfection (and HIV / TB) process of a pregnant woman. In a retrospective discussion of medical tactics marked the main points of contention in the conduct of pregnant women with coinfection (HIV / TB), an analysis of the adequacy and the need for X-ray examination of the patient, the effectiveness of the treatment process coinfection process. The case demonstrates the ability of HIV-infected effectively treat tuberculosis and healthy baby female patient with active tuberculosis with timely and adequate combination therapy (antiretroviral and anti-tuberculosis)