A combination of three muramyl peptides derived from gramnegative bacteria in immunotherapy of chronic pyodermia

The aim of the present study was to evaluate the clinical efficacy of a standardized combination of three muramyl peptides containing a residue of meso-diaminopimelic acid (Polymuramyl), as well as effects of this immunomodulator on the lymphocyte subpopulation profile, function of circulating neutrophils, and concentrations of serum immunoglobulins in the patients with chronic recurrent pyoderma. Thirty-five men (34.5±10 years) with exacerbation of chronic pyoderma (osteofolliculitis, folliculitis, sycosis, furunculosis) were randomized into two groups matched by age and clinical manifestations of the disease. In the comparison group (n = 17), the patients received standard treatment. In the main group (n = 18), in addition to the same standard treatment, the patients received intramuscular injections of Polymuramyl at a dose of 200 mg daily from day 1 to 5 of the study. The overall assessment of the treatment efficacy was performed on the day 14, and at 1 and 6 months of observations. Induction and maintenance of complete clinical remission were assessed as “significant improvement”; induction and maintenance of partial remission were considered to be “improvement”; persistent signs of skin inflammation and lack of remission were assessed as “lack of effect”. Immunological parameters were studied on days 0 and 14, and then at 1 and 6 months of the study. Addition of Polymuramyl to the standard treatment caused a marked tendency towards increased proportion of the patients with «significant improvement» or «improvement» on the day 14: total ratio of the patients with any clinical improvement was 24% higher, and the relative number of the patients with "lack of effect" was five-fold lower than in the comparison group (p=0.076). A trend towards improved clinical efficacy, according to the above criteria, was maintained after 1 and 6 months of the study. At 6 months of the follow-up, the proportion of patients without pustules/furuncles in the main group (9 out of 18) exceeded that in the comparison group (3/17, p = 0.047). Significant inter-group differences and dynamics of indicators of neutrophil functions, subpopulation composition of lymphocytes and concentrations of immunoglobulins in serum were not detected. However, in the main group after the 6-month observation, there was an upward trend in the absolute number of T-cells due to CD3+CD4+ subpopulation, as well as serum IgA concentration. The results of this study are in accordance with previously published data, thus indicating the ability of Polymuramyl to accelerate regression of clinical manifestations of chronic pyoderma and induce sustained remission of this disease. At the same time, the design of present investigation and the timing of taking biological samples for laboratory tests did not allow to register significant changes in most of the studied systemic immunological parameters under the influence of immunomodulator, except for the previously described modulation at the level of pro- and anti-inflammatory cytokines

Anti-inflammatory and immunomodulating effects of the bacterial lysate in the <em>in vivo</em> models of aseptic lymphadenitis and pneumococcal pneumonia

Bacterial lysates may produce immunoregulatory effects in the inflammatory diseases that are not directly caused by infectious agents; they may also stimulate the immune response against pathogens which are not a part of the lysate composition. Imudon® is a polyvalent bacterial lysate that is available in orodispersible tablets. However, the influence of this drug product on aseptic inflammation and immune defense against the infectious agents, the antigens of which are not contained in this preparation have not been studied so far. The aim of this study, therefore, was to determine the anti-inflammatory and immunomodulating effects of Imudon® using the models of aseptic lymphadenitis (in Wistar rats) and pneumococcal pneumonia (in Balb/c mice), i.e., the conditions not related to the specific components of the bacterial lysate. Lymphadenitis was induced in rats by administration of λ-carrageenan into a cervical lymph node via an open operative approach. Whereas pneumonia was induced in mice by administering Streptococcus pneumoniae suspension intranasally. The choice of pneumococcus was determined by the absence of pneumococcal antigens in Imudon®, i.e., it cannot be a direct inducer of adaptive immune response against pneumococcal infection. Imudon® was administered intragastrically as a crushed tablet suspension following a therapeutic-preventive regimen (for 14 days daily until the induction of inflammation and for 3 [in the lymphadenitis model] or 5 days [in the model of pneumonia] in three doses thereafter). In the lymphadenitis model, Imudon® demonstrated both local and systemic anti-inflammatory responses manifested in the reduced number of circulating leucocytes and lower TNFα levels and by ameliorated histological features of inflammation in the operated lymph node. In rats, the anti-inflammatory effect was most pronounced when the product was administered at a dose of 2.2 mg/kg (equivalent to a human therapeutic dose) and 6.6 mg/kg. In the model of pneumonia, administration of Imudon® at 4.44 mg/kg (equivalent to a human therapeutic dose) and 13.32 mg/kg demonstrated a trend towards increased survival rate as compared to the control group. On Day 5 after infection Imudon® (4.44 and 13.32 mg/kg) decreased significantly the severity of inflammation and bacterial titer in the lungs. The titer of anti-pneumococcal immunoglobulins A in the bronchoalveolar lavage fluid were found to be higher in the Imudon® treated group (13.32 mg/kg) compared to control group. The results of this study showed high antiinflammatory and immunomodulatory activities of Imudon® and provided an insight into the mechanisms that underlie the clinical effects of this drug in various inflammatory diseases

Распространенность, клиническое и прогностическое значение полиморфизма генов II, V факторов свертывания крови и метилентетрагидрофолатредуктазы у пациентов с хронической болезнью почек

The aim of the investigation was to study the prevalence, clinical and prognostic values of polymorphism of genes II, V factors of blood coagulation and methylenetetrahydrofolate reductase in patients with chronic kidney disease. Examination was performed on 90 patients with diabetic nephropathy (DN) and 180 patients with chronic glomerulonephritis (CG). In addition to complete clinical and instrumental examination accepted in specialised clinic, with the help of polymerase chain reaction diagnostics of polymorphism of the referred above genes (samples of genomic DNA were obtained from peripheral blood leukocytes) was conducted. It was found that the protrombogenic mutations under investigation which are detected in patients with DN and CG more often than in healthy subjects are associated with development of hypercoagulation syndrome and higher risk of renal failure.Изучены распространенность, клиническое и прогностическое значение полиморфизма генов II, V факторов свертывания крови и метилентетрагидрофолатредуктазы у пациентов с хронической болезнью почек. Обследовано 90 пациентов с диабетической нефропатией (ДН) и 180 больных хроническим гломерулонефритом (ХГН). Наряду с полным клиническим и инструментальным обследованием, принятым в специализированной клинике, с помощью метода полимеразной цепной реакции выполнена диагностика полиморфизма указанных генов (образцы геномной ДНК получали из лейкоцитов периферической крови). Установлено, что изучаемые протромбогенные мутации встречаются у больных ДН и ХГН с большей частотой, чем среди здоровых лиц, ассоциированы с развитием гиперкоагуляционного синдрома и повышением риска почечной недостаточности

НЕСПЕЦИФИЧЕСКИЕ МЕХАНИЗМЫ ПРОГРЕССИРОВАНИЯ ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК

The authors of the review have analyzed papers published on the problem of pathogenesis chronic kidney disease (CKD), which the experts of the K/DOQI (Kidney Disease Outcomes Quality Initiative) Advisory Board (National Kidney Foundation, USA) is defined as the presence of kidney damage or decreased level of kidney function for three months or more, irrespective of diagnosis. It is shown that the specific mechanisms which result directly from the nature of the disease, completely determine the course of CKD in its initial stage, whereas further reduction in the number of intact nephrons, cascade is initiated univer-sal for all of nephropathy pathological processes, culminating in the formation of nephrosclerosis, often even if the reason that caused the initial damage to the nephrons is eliminated: hyperfiltration, hypercoag-ulability, impaired renal transport protein, changes in the expression of mediators of cell damage, meta-bolic and endocrine mechanisms, polymorphism of genes controlling the expression of nephrotropic bio-logically active substances. Analyzed published data demonstrate that renal protection strategy (complex therapies aimed at the inhibition of the irreversible deterioration of kidney function and affect common to all of nephropathy mechanisms of progression) can slow the progression of CKD. Авторы обзора анализируют работы, опубликованные по проблеме патогенеза хронической болез-ни почек (ХБП), которую эксперты Консультативного совета инициативы качества лечения забо-левания почек Национального почечного фонда США определяют как наличие почечного повре-ждения или сниженного уровня функции почек на протяжении не менее 3 мес независимо от этио-логии. Показано, что специфические механизмы, обусловленные непосредственно характером заболевания, целиком определяют течение ХБП лишь в начальной стадии, тогда как при редукции числа интактных нефронов инициируется каскад универсальных для всех нефропатий патологиче-ских процессов, завершающихся формированием нефрофиброза, даже если причина, вызвавшая первоначальное повреждение нефронов устранена: гиперфильтрация, гиперкоагуляция, наруше-ние почечного транспорта белка, изменение экспрессии медиаторов повреждения клеток, метабо-лические и эндокринные механизмы, полиморфизм генов, контролирующих экспрессию нефро-тропных биологически активных веществ. Опубликованные данные демонстрируют, что нефро-протективная стратегия (комплекс методов лечения, направленных на торможение необратимого ухудшения функции почек и воздействующих на общие для всех нефропатий механизмы прогрес-сирования) позволяет замедлить развитие ХБП