Consensus concept of modern effective therapy for Duchenne muscular dystrophy

Duchenne muscular dystrophy is a genetic orphan neuromuscular disease caused by a mutation in the DMD gene encod‑ ing the protein dystrophin. As a result of developing and progressive muscle damage and atrophy, childrenlose the abil‑ ity to walk, develop respiratory and cardiac disorders. The core elements of good care standards are early diagnosis, prevention and treatment of osteoporosis, daily physical therapy, regular rehabilitation, glucocorticosteroids, and control of heart andlung function. The clinical effect of new targeted pathogenetic therapies for Duchenne muscular dystrophy, restoring synthesis of full or truncated dystrophin, depend on their appropriate combination with existing standards of care. © 2023 ABV-Press Publishing House. All rights reserved

Основополагающее значение понятий «амбулаторность» и «неамбулаторность» в комплексной оценке состояния пациентов с мышечной дистрофией Дюшенна

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease due to a mutation in the gene encoding dystrophin synthesis. In patients, muscle damage and atrophy progresses, the ability to move independently decreases as well as respiratory and cardiac functions. At various stages of the disease, different methods of care and treatment of patients with DMD are used. The clinical effect of new methods of DMD target therapy may depend on the stage of development of the disease (ambulatory or non‑ambulatory). To date, there are no unified criteria for assessing the status of a patient in terms ambulatory. In clinical trials and real clinical practice, different approaches are used to assess the patient’s status. However, the conclusion about the functional capabilities is critical for patients with DMD as approaches in management of patients in ambulatory and non‑ambulatory stages differ significantly. This necessitates expert consensus to achieve consistency and avoid any of discrepancies on that issue.The paper reviews the available published data on the concepts of “ambulatory” and “non‑ambulatory” used in clinical trials, real clinical practice, international standards and recommendations. As a conclusion of this analysis, it is proposed in real clinical practice to interpret “ambulation” in DMD patients as ability to walk without the use of assistive devices and without specifying the distance and time, and “non‑ambulation” as condition in which the patient is forced to constantly use a wheelchair both indoors and outdoors.Мышечная дистрофия Дюшенна (МДД) – фатальное нервно‑мышечное заболевание, обусловленное мутацией гена, кодирующего белок дистрофин. В результате развивающегося и прогрессирующего повреждения и атрофии мышц пациенты теряют способность к самостоятельному передвижению, у них развиваются респираторные и кардиологические нарушения. На разных стадиях МДД используются разные методы ведения. Клинический эффект новых методов таргетной терапии МДД может зависеть от стадии болезни на момент назначения лечения: амбулаторной, когда пациент ходит самостоятельно, или неамбулаторной, когда способность к самостоятельной ходьбе утрачена. Сегодня нет единых критериев статуса пациента с точки зрения амбулаторности, а в клинических исследованиях и реальной практике используются разные подходы к ее оценке. Тем не менее определение понятий «амбулаторность» и «неамбулаторность» критично для пациентов с МДД, так как подходы к ведению пациентов в амбулаторной и неамбулаторной стадии болезни различны. В статье представлены обзор, сравнение и анализ определений «амбулаторность» и «неамбулаторность», использованных в клинических исследованиях, реальной медицинской практике, международных стандартах и рекомендациях.По итогам анализа предлагается в реальной клинической практике трактовать амбулаторность больных МДД как способность ходить без использования вспомогательных средств и без указания дистанции и времени, а потерей амбулаторности считать состояние, при котором пациент вынужден постоянно использовать инвалидное кресло для передвижения как вне дома, так и в домашних условиях

The core structure of the lipopolysaccharide from the causative agent of plague, Yersinia pestis.: Carbohyd.Res.

NRC publication: Ye

Effect of Rifaximin and a Multi-Strain Probiotic on the Intestinal Microbiome and Cardiovascular Risk Indicators in Patients with Coronary Heart Disease

Aim. To assess the effect of rifaximin and a multi-strain probiotic on the intestinal microbiome and the indicators of cardiovascular risk in patients with coronary heart disease (CHD).Materials and methods. A study conducted during the 2016–2019 period included 120 people over 50 years old divided into 3 groups. Group 1 comprised patients with coronary heart disease receiving standard treatment. Group 2 comprised patients with coronary heart disease receiving additionally a probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) within 28 days. Group 3 comprised CHD patients receiving rifaximin for 7 days followed by addition of the multi-strain probiotic under test for 21 days. Group 4 consisted of healthy individuals, comparable in age and sex with the examined CHD patients. In group 4, blood and stool tests were performed once to provide a comparison with group 1. TMAO concentration was determined using liquid chromatography–mass spectrometry. To study the composition of fecal microflora, 16S sequencing was used followed by a graphical representation of the results. The results were analysed using the IBM SPSS 22.0 statistical data processing software.Results. An additional administration of the probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) is found to have no effect on the lipid profile and the platelet aggregation rate. Rifaximin therapy reduced the amount of total cholesterol, low density lipoproteins (LDL), very low density (VLDL) lipoproteins and triglycerides (p <0.05), although not affecting the level of high density lipoproteins (HDL). TMAO showed a statistically insignificant (p>0.05) downward trend in all groups. The composition of the fecal microbiota, at the end of administration of the probiotic, showed an increase in the proportion of bacteria of the Streptococcaceae, Lactobacillaceae, Enterobacteriaceae families and a decrease in the Ruminococcaceae family (p>0.05). After rifaximin therapy, a decrease in the proportion of bacteria of the Clostridiaceae (p <0.05) and Peptostreptococcaceae (p <0.05) families, a decrease in Enterobacteriaceae (p > 0.05) family and a decrease in the Clostridium and Escherichia/Shigella (p > 0.05) genera was observed. The use of the probiotic after a course of treatment with rifaximin did not have a significant effect on the composition of the microflora. In general, the high variability of fecal microbiota between different patients (significantly superior to intergroup differences) does not allow us to draw unambiguous conclusions.Conclusions. The use of a multi-strain probiotic as an additional therapy in patients with coronary heart disease within 28 days did not have a significant effect on lipid metabolism, TMAO level and the composition of fecal microflora. The consecutive use of rifaximin and the probiotic had a beneficial effect on such factors as lipid metabolism (decrease in the level of total cholesterol, LDL, VLDL, triglycerides), but did not affect the concentration of TMAO and the composition of the intestinal microflora in patients with coronary heart disease

Effect of Rifaximin and a Multi-Strain Probiotic on the Intestinal Microbiome and Cardiovascular Risk Indicators in Patients with Coronary Heart Disease

Aim. To assess the effect of rifaximin and a multi-strain probiotic on the intestinal microbiome and the indicators of cardiovascular risk in patients with coronary heart disease (CHD).Materials and methods. A study conducted during the 2016–2019 period included 120 people over 50 years old divided into 3 groups. Group 1 comprised patients with coronary heart disease receiving standard treatment. Group 2 comprised patients with coronary heart disease receiving additionally a probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) within 28 days. Group 3 comprised CHD patients receiving rifaximin for 7 days followed by addition of the multi-strain probiotic under test for 21 days. Group 4 consisted of healthy individuals, comparable in age and sex with the examined CHD patients. In group 4, blood and stool tests were performed once to provide a comparison with group 1. TMAO concentration was determined using liquid chromatography–mass spectrometry. To study the composition of fecal microflora, 16S sequencing was used followed by a graphical representation of the results. The results were analysed using the IBM SPSS 22.0 statistical data processing software.Results. An additional administration of the probiotic (Bifidobacterium bifidum no less than 1x109 CFU; Bifidobacterium longum no less than 1x109 CFU; Bifidobacterium infantis no less than 1x109 CFU; Lactobacillus rhamnosus no less than 1x109 CFU) is found to have no effect on the lipid profile and the platelet aggregation rate. Rifaximin therapy reduced the amount of total cholesterol, low density lipoproteins (LDL), very low density (VLDL) lipoproteins and triglycerides (p <0.05), although not affecting the level of high density lipoproteins (HDL). TMAO showed a statistically insignificant (p>0.05) downward trend in all groups. The composition of the fecal microbiota, at the end of administration of the probiotic, showed an increase in the proportion of bacteria of the Streptococcaceae, Lactobacillaceae, Enterobacteriaceae families and a decrease in the Ruminococcaceae family (p>0.05). After rifaximin therapy, a decrease in the proportion of bacteria of the Clostridiaceae (p <0.05) and Peptostreptococcaceae (p <0.05) families, a decrease in Enterobacteriaceae (p > 0.05) family and a decrease in the Clostridium and Escherichia/Shigella (p > 0.05) genera was observed. The use of the probiotic after a course of treatment with rifaximin did not have a significant effect on the composition of the microflora. In general, the high variability of fecal microbiota between different patients (significantly superior to intergroup differences) does not allow us to draw unambiguous conclusions.Conclusions. The use of a multi-strain probiotic as an additional therapy in patients with coronary heart disease within 28 days did not have a significant effect on lipid metabolism, TMAO level and the composition of fecal microflora. The consecutive use of rifaximin and the probiotic had a beneficial effect on such factors as lipid metabolism (decrease in the level of total cholesterol, LDL, VLDL, triglycerides), but did not affect the concentration of TMAO and the composition of the intestinal microflora in patients with coronary heart disease

Temperature-dependent variations and intraspecies diversity of the structure of the lipopolysaccharide of Yersinia pestis.: Biochemistry

NRC publication: Ye

Консенсус по концепции современной эффективной терапии мышечной дистрофии Дюшенна

Duchenne muscular dystrophy is a genetic orphan neuromuscular disease caused by a mutation in the DMD gene encoding the protein dystrophin. As a result of developing and progressive muscle damage and atrophy, children lose the ability to walk, develop respiratory and cardiac disorders. The core elements of good care standards are early diagnosis, prevention and treatment of osteoporosis, daily physical therapy, regular rehabilitation, glucocorticosteroids, and control of heart and lung function. The clinical effect of new targeted pathogenetic therapies for Duchenne muscular dystrophy, restoring synthesis of full or truncated dystrophin, depend on their appropriate combination with existing standards of care.Мышечная дистрофия Дюшенна – генетическое орфанное нервно‑мышечное заболевание, обусловленное мутацией гена DMD, кодирующего белок дистрофин. В результате развивающегося и прогрессирующего повреждения и атрофии мышц дети теряют способность ходить, у них развиваются респираторные и кардиологические нарушения. При условии ранней диагностики медицинская помощь, направленная на максимально продолжительное сохранение амбулаторности пациента, при терапии глюкокортикостероидами и реабилитационных мероприятиях для предупреждения сердечно‑легочных осложнений и остеопороза существенно меняет траекторию развития заболевания. Эффективность новых препаратов генной таргетной терапии миодистрофии Дюшенна, частично восстанавливающих синтез полноразмерного или редуцированного дистрофина, зависит от их своевременного и адекватного использования в сочетании с комплексной медицинской помощью, рекомендованной для данной нозологии