Functional Comparison of Innate Immune Signaling Pathways in Primates

Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host–virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV–interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Efficacy of Physiologically Active nutrients in the Treatment of Asthenic Disorders in Patients with Chronic Diffuse Liver Diseases

Over the period after an exacerbation of chronic liver diseases, patients often retain common symptoms (weakness or fatigue, bad mood, sleep disorder, vegetative disorders — asthenic syndrome). In the context of prevention and treatment of these symptoms, such nutraceutical products as enriched foods in the form of tablets, sachets, etc, have been increasingly attracting research attention.Aim. To study the efficacy of the “Hepato Smart” nutraceutical product for the treatment of asthenic syndrome in outpatients suffering from chronic diffuse liver diseases with compensated function and functional disorders of the gallbladder over the period after exacerbation.Materials and methods. The study included 50 patients, with 41 of them having completed the program. The nutraceutical product (curcumin, piperine, tanshinone IIA, choline; standardized for curcumin and choline) was assigned 1 pill 3 times a day with meals for 4 weeks. To objectify common symptoms, we used a D-FIS questionnaire (Daily Fatigue Impact Scale), a 4DSQ Four-Dimensional Symptom Questionnaire for assessing distress, depression, anxiety and somatization, and a SF-36 questionnaire for assessing the quality of life.Results. Following 4 weeks of the “Hepato Smart” course, a statistically significant decrease in fatigue was noted by D-FIS scores (p = 0.003), as well as a decrease in the level of distress, depression, anxiety and somatization by 4DSQ scores (p = 0.005; p = 0.006; p = 0.003; p = 0.003, respectively). The quality of patients’ life according to the SF36 questionnaire also improved due to both physical and psychological components (p = 0.003). 16 patients continued taking the preparation for another 8 weeks to maintain the achieved result. As an additional effect, the disappearance of pain in the right hypochondrium was noted in those cases when patients presented this complaint at the time of inclusion in the observation program. The safety profile was good, 1/3 of the patients noted the appearance of heartburn, which was eliminated when taking the product with food.Conclusion. The “Hepato Smart” nutraceutical product improves the general condition of patients with chronic diffuse liver diseases and functional disorders of the gallbladder due to a significant reduction in fatigue and anxiety. It also improves the quality of patients’ life due to the physical and mental components of health

Efficacy of Physiologically Active nutrients in the Treatment of Asthenic Disorders in Patients with Chronic Diffuse Liver Diseases

Over the period after an exacerbation of chronic liver diseases, patients often retain common symptoms (weakness or fatigue, bad mood, sleep disorder, vegetative disorders — asthenic syndrome). In the context of prevention and treatment of these symptoms, such nutraceutical products as enriched foods in the form of tablets, sachets, etc, have been increasingly attracting research attention.Aim. To study the efficacy of the “Hepato Smart” nutraceutical product for the treatment of asthenic syndrome in outpatients suffering from chronic diffuse liver diseases with compensated function and functional disorders of the gallbladder over the period after exacerbation.Materials and methods. The study included 50 patients, with 41 of them having completed the program. The nutraceutical product (curcumin, piperine, tanshinone IIA, choline; standardized for curcumin and choline) was assigned 1 pill 3 times a day with meals for 4 weeks. To objectify common symptoms, we used a D-FIS questionnaire (Daily Fatigue Impact Scale), a 4DSQ Four-Dimensional Symptom Questionnaire for assessing distress, depression, anxiety and somatization, and a SF-36 questionnaire for assessing the quality of life.Results. Following 4 weeks of the “Hepato Smart” course, a statistically significant decrease in fatigue was noted by D-FIS scores (p = 0.003), as well as a decrease in the level of distress, depression, anxiety and somatization by 4DSQ scores (p = 0.005; p = 0.006; p = 0.003; p = 0.003, respectively). The quality of patients’ life according to the SF36 questionnaire also improved due to both physical and psychological components (p = 0.003). 16 patients continued taking the preparation for another 8 weeks to maintain the achieved result. As an additional effect, the disappearance of pain in the right hypochondrium was noted in those cases when patients presented this complaint at the time of inclusion in the observation program. The safety profile was good, 1/3 of the patients noted the appearance of heartburn, which was eliminated when taking the product with food.Conclusion. The “Hepato Smart” nutraceutical product improves the general condition of patients with chronic diffuse liver diseases and functional disorders of the gallbladder due to a significant reduction in fatigue and anxiety. It also improves the quality of patients’ life due to the physical and mental components of health

Efficacy of drugs most commonly prescribed at functional gastrointestinal diseases (functional dyspepsia syndrome and irritable bowel syndrome) observational study results

Aim of investigation. To estimate the frequency of prescription of motility regulators and probiotics in the functional gastrointestinal diseases. To define efficacy of these agents according to results of «7×7» questionnaire (7 symptoms per 7 days) at treatment of functional dyspepsia (FD), irritable bowel syndrome (IBS) and combination of these diseases. Material and methods. Overall 502 patients aged 18 to 65 with symptoms complying to the «Rome-III» criteria and absence of «alarm symptoms» with the preliminary diagnosis of the functional gastrointestinal disorder: IBS, FD or combination of these diseases were started. During the first visit to the doctor patient was proposed to complete «7×7» questionnaire for baseline assessment of presence and severity of symptoms typical for FD and IBS. Later all patients underwent a set of laboratory and instrumental tests required according to «Guidelines on diagnostics and treatment of the irritable bowel syndrome in adults» of the Russian gastroenterological association and Russian Association of coloproctology and to «Clinical guidelines on diagnostics and treatment of the functional dyspepsia» of the Russian gastroenterological association. After primary investigation 108 patients were excluded from the study due to diagnosis change. Primary documentation data of 11 patients were unsuitable for statistical processing. The analysis of primary documentation and results symptom assessment of 383 patients with verified diagnosis of functional gastrointestinal disease by «7×7» questionnaire was carried out. Treatment algorithms, their conformity to establish diagnosis and efficacy were analyzed as well. Results. Motility regulator trimebutine was prescribed to 258 (67,4%) patients with various diseases: 30 (60%) IBS patients, 67 (73,6%) FD patients, and 157 (64,8%) patients with combination of both disorders. Modes of treatment which included trimebutine demonstrated higher efficacy in comparison to treatment algorithms, which included antispasmodic medications with respect to relief of all symptoms (according to the «7×7» questionnaire data), except for constipation and in disorders of stool consistency (firm stool): efficacy of trimebutinecontaining moods for those symptoms was comparable to those with application of spasmolytic drugs. Probiotic agents with various content in combination to other group drugs were prescribed to 127 patients: 29 FD patients (22,3%); 20 IBS patients (14,5%), and 78 FD to IBS combination (60%). It is established that presence of probiotic in the treatment mode leads to significant reduction in main symptoms severity typical both for FD and IBS according to the «7×7» questionnaire

Antioxidants in the Treatment of Chronic Diffuse Liver Diseases (the Results of the “MAXAR” Observational Program)

In the Russian Federation, liver diseases are most frequently represented by two their nosological forms, i.e., nonalcoholic and alcoholic fatty liver disease (NAFLD and ALD). A successful management of such patients, along with improving the functional state of the liver, requires a careful analysis of patients’ nonspecific complaints. In particular, it is important to investigate asthenic syndrome, which can indirectly result in the exacerbation of liver diseases, thus incurring additional economic costs to national healthcare systems. Therefore, the elucidation of the nature of asthenic syndrome and a search for methods for its resolution seem to be highly relevant research tasks.Aim. This study aims to investigate the effect of the antioxidant drug (the extract of the Amur maackia wood) on the organic and functional components of asthenic syndrome in patients with NAFLD and ALD, who do not show signs of the disease decompensation. Materials and methods. An observational program was carried out under the conditions of daily clinical practice in three Russian cities: Moscow, Chelyabinsk and Vladivostok. 80 patients (40 with NAFLD, 40 with ALD) were comprehensively examined according to a developed program. A number of laboratory indicators that reveal inflammatory processes in the liver were studied, including leukocytes, ESR, ALT, AST, GGTP and CRP. The patients’ psycho-emotional status was assessed using a Daily Fatigue Impact Scale (D-FIS) and a four-dimensional scale for assessing distress, depression, anxiety and somatisation (4DSQ). Results. According to the D-FIS questionnaire, all the patients showed fatigue. According to the 4DSQ questionnaire, a correlation of distress with the level of laboratory indicators was revealed among all the patients. No such a correlation was noted for depression and anxiety in the patients with NAFLD. On the contrary, in the case of ALD, all psycho-emotional disorders (except for somatisation) were positively correlated with the markers of inflammation. It is shown that asthenic syndrome in patients with both NAFLD and ALD has a complex origin, being associated both with inflammatory processes in the liver and psycho-emotional disorders. In all cases under study, the prescription of the preparation led to a decrease in the studied laboratory indicators (inflammation markers) and an increase in the patients’ psycho-emotional status. The latter improvement was manifested in the reduction of distress, depression, anxiety and somatisation, according to the 4DSQ questionnaire, as well as in the reduction of fatigue, according to the D-FIS questionnaire.Conclusion. The results of the observational program have shown that patients with NAFLD and ALD frequently experience such components of asthenic syndrome as distress, depression, anxiety, somatisation and fatigue. The prescription of the preparation is found to result in a decrease in laboratory inflammatory indicators. In addition, the preparation is determined to positively affect the components of asthenic syndrome in patients with NAFLD and ALD. In the course of the treatment, no clinically significant side effects were documented