ИНДЕКС МАССЫ ТЕЛА И ФОРМИРОВАНИЕ СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИИ У ПАЦИЕНТОВ, ПОЛУЧАЮЩИХ ЛЕЧЕНИЕ СУПРЕССИВНЫМИ ДОЗАМИ ЛЕВОТИРОКСИНА

One of the most important problems of a long monitoring of the patients operated for thyroid carcinoma and receiving suppressive therapy with levothyroxine is the prevention of the adverse effects of treatment on the cardiovascular system. The purpose of the work is to identify the features of formation of symptoms and signs of cardiovascular diseases, as well as heart rhythm abnormalities in young patients receiving suppressive therapy with levothyroxine depending on their body mass index (BMI). Changes in the heart rate variability in patients with tachycardia and high blood pressure are studied. It is shown that patients with normal and overweight have alternative tendencies in the changes of heart rate and the formation of cardiovascular diseases.Одной из важнейших проблем длительного мониторинга пациентов, прооперированных по поводу карциномы щитовидной железы и получающих супрессивную терапию левотироксином, является профилактика побочных влияний лечения на сердечно-сосудистую систему. Цель работы – выявить особенности формирования симптомов и признаков болезней системы кровообращения, а также отклонений сердечного ритма у молодых пациентов, получающих супрессивную терапию левотироксином более 10 лет, в зависимости от их индекса массы тела. Изучены сдвиги показателей вариабельности сердечного ритма у пациентов с тахикардией и повышенным артериальным давлением. Показано, что у пациентов с нормальной и избыточной массой тела существуют альтернативные тенденции в изменениях сердечного ритма и формировании болезней системы кровообращения. Пациенты, имеющие избыточную массу тела, являются группой риска по развитию артериальной гипертензии при снижении вариабельности сердечного ритма и повышении индекса централизации, а также тонуса симпатической вегетативной нервной системы за пределы нормы. Пациенты с нормальной массой тела, имеющие повышенную вариабельность сердечного ритма, являются группой риска по развитию тахикардии и аритмии

Факторы риска микробиологической неэффективности комплексной пробиотической терапии в отношении облигатной микрофлоры кишечника больных туберкулезом с множественной лекарственной устойчивостью возбудителя

The aim of the work was to identify risk factors for the absence of a microbiological effect when using complex probiotic therapy in patients with drug-resistant tuberculosis.Material and methods. The object of the study was 30 patients with tuberculosis in the course of anti-tuberculosis therapy, who received a course of complex probiotic therapy. The patients were divided into groups according to the microbiological effect of using the probiotic against Bifido and Lactobacterium spp .: Group 1 – restoration of Lactobacterium spp. Happened, 2 – did not happen, 1A – recovery of Bifidobacterium spp. Happened, 1B did not happen. With the help of statistical processing of the material, the main risk factors for reducing its effectiveness have been identified.Research results. Among all factors (gender, social status, HIV infection, immunodeficiency, smoking, alcohol dependence, clinical form of tuberculosis and anti-tuberculosis drugs taken), the risk of reducing the efficiency of the Lactobacterium spp. in tuberculosis patients it is shown in males (OR 2.500, p = 0.029) over the age of 50 (p = 0.008). However, a significant decrease in the effectiveness of complex probiotic therapy to restore the pool of Lactobacterium spp. in the intestinal biotope is statistically significant due to the male sex (OR 8,000, p = 0.013 and the number of CD4 + lymphocytes (p = 0.005).Conclusion. The main risk factors for a decrease in the rate of recovery of the pool of Lactobacterium spp. in patients with multidrug-resistant tuberculosis, the pathogen was male and female, and the recovery of the Bifidobacterium spp. depended on the male sex and the severity of immunodeficiency in the presence of HIV infection.Целью работы являлось выявление факторов риска отсутствия микробиологического эффекта при применении комплексной пробиотической терапии у пациентов с лекарственно резистентным туберкулезом.Материалы и методы. Объектом исследования явились 30 пациентов с туберкулезом в процессе противотуберкулезной терапии, получивших курс комплексной пробиотической терапии. Пациенты были разделены на группы согласно микробиологическому эффекту применения пробиотика в отношении Bifido- и Lactobacterium spp.: 1 группа – восстановление Lactobacterium spp. произошло, 2 – не произошло, 1А – восстановление Bifidobacterium spp. произошло, 1Б – не произошло. При помощи статистической обработки материала определены основные факторы риска снижения его эффективности.Результаты. Среди всех факторов (пол, социальный статус, ВИЧ-инфекция, иммунодефицит, курение, зависимость от алкоголя, клиническая форма туберкулеза и принимаемые противотуберкулезные препарты) риск снижения эффективности восстановления пула Lactobacterium spp. у больных туберкулезом показан у лиц мужского пола (ОШ 2,500, р=0,029) в возрасте старше 50 лет (р=0,008). Однако значительное снижение эффективности комплексной пробиотической терапии на восстановление пула Lactobacterium spp. в кишечном биотопе статистически значимо обусловлено мужским полом (ОШ 8,000, р=0,013 и количеством CD4+лимфоцитов (р=0,005).Заключение. Основными факторами риска снижения скорости восстановления пула Lactobacterium spp. у больных туберкулезом с множественной лекарственной устойчивостью возбудителя явились мужской пол и возраст, а восстановление пула Bifidobacterium spp. зависело от мужского пола и выраженности иммунодефицита при наличии ВИЧ-инфекции

Effectiveness of mebeverine in patients with post-cholecystectomy gastrointestinal spasm: results of prospective observational program “odyssey”

Aim: to assess the effectiveness of mebeverine 200 mg BID in patients with post-cholecystectomy gastrointestinal spasm not requiring surgical treatment. Materials and methods. 218 patients were included in 16 clinical centers in 14 cities in Russia. All patients had post-cholecystectomy gastrointestinal spasms, not requiring surgical treatment and received mebeverine (Duspatalin®) 200 mg BID. The observational assessment period lasted from the moment of their inclusion into the study up to 6 weeks post inlusion. The therapy results were evaluated using visual analog scales (GPA and 11-point numeric rating scale) by patient self-assessment of the dynamics of spasm/discomfort and other post-cholecystectomic gastrointestinal symptoms after 2 and 6 weeks of treatment. Gastrointestinal Quality of Life Index (GIQLI) was used to assess patient quality of life. Results and discussion. All 218 patients completed the 2-week mebeverine treatment course, 101 of them finished the 6-week course (“prolonged population”). Significant positive changes in the relief of abdominal pain and dyspepsia were noted as well as normalization of stool frequency and consistency. A more marked change in values was observed during prolonged (up to 6 weeks) therapy. Both 2-week and 6-week mebeverine courses led to a normalization of patient quality of life. After 6 week therapy, an effect of mebeverine on the quality of life 91% of patients was observed comparable to cholecystectomy itself, speficially related to the quality of life subscore ‘symptoms’. Conclusion. The results of our study demonstrate that mebeverine (Duspatalin®) therapy leads to an effective elimination of clinical symptoms associated with post-cholecystectomy GI-spasm disorders, like abdominal pain, symptoms of dyspepsia and stooldisorders. A more marked change in values was observed during prolonged (up to 6 weeks) therapy

Expression of tumor growth related genes in IRE1 knockdown U87 glioma cells: effect of hypoxia

We have studied the effect of IRE1 signaling enzyme knockdown as well as hypoxia on the expression of genes encoding the important tumor growth related proteins (BRCA1, DEK, BCL2L1, COL6A1, TPD52, HOMER3, and GNPDA1) in U87 glioma cells. It was shown that the expression level of breast cancer 1 early onset (BRCA1) and tumor protein D52 (TPD52) mRNAs are strongly up-regulated in U87 glioma cells by down-regulation of IRE1 expression in comparison with the control cells. At the same time the expression level of collagen, type VI, alpha 1 (COL6A1), DEK oncogene (DEK), glucosamine-6-phosphate deaminase 1 (GNPDA1) and homer homolog 3 (HOMER3) was significantly down-regulated in glioma cells under these experimental conditions. It was also shown that hypoxia up-regulated the expression level of COL6A1 and TPD52 mRNAs and down-regulated – BRCA1, DEK, and GNPDA1 mRNAs in control glioma cells and that down-regulation of IRE1, which control cell proliferation and tumor growth, modified the effect of hypoxia on the expression of COL6A1, DEK, BCL2L1, HOMER3, and GNPDA1 genes. The present study demonstrated that hypoxia affected the expression of most studied genes in IRE1-dependent manner

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

The expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with ERN1 (endoplasmic reticulum to nucleus signaling 1) loss of function as well as upon glutamine deprivation was studied. It was shown that glutamine deprivation down-regulated the expression level of ATF6 (activating transcription factor 6), EIF2AK3/PERK (eukaryotic translation initiation factor 2 alpha kinase 3), GLO1 (glyoxalase I), BIRC5 (baculoviral IAP repeat-containing 5), and RAB5C (RAB5C, a member of RAS oncogene family) mRNAs in control glioma cells. At the same time, the expression level of HSPB8 (heat shock 22kDa protein 8) and HSPA5/GRP78 (heat shock protein family A (Hsp70) member 5) mRNAs was resistant to glutamine withdrawal in these glioma cells. It was also shown that inhibition of ERN1, which controled cell proliferation and tumor growth, modified the effect of glutamine deprivation on the expression levels of most studied genes in U87 glioma cells: up-regulated the expression of ATF6 and HSPA5 genes and enhanced sensitivity of EIF2AK3 and BIRC5 genes to glutamine withdrawal. Furthermore, the expression of all studied genes, except EIF2AK3, was down-regulated in ERN1 knockdown glioma cells in the presence of glutamine. It was demonstrated that glutamine deprivation affected the expression of most studied genes in ERN1 depen­dent manner and that these changes possibly contributed to the suppression of glioma growth from cells without ERN1 signaling enzyme function

Association of vascular stiffness and geriatric syndromes in hypertensive elderly patients

Aim. To study the relationship of vascular stiffness (cardio-ankle vascular index (CAVI)) with frailty and other geriatric syndromes in hypertensive elderly patients.Material and methods. The study included 160 patients aged 60 to 101 years with verified stage I-III hypertension. The previous therapy was assessed. A comprehensive geriatric assessment was performed with functional and neuropsychological tests to identify geriatric syndromes. Vascular stiffness was assessed by VaSera-VS-1500 vascular screening system (FUKUDA DENSHI, Japan) with determination of the CAVI.Results. The mean age of the patients was 77,2±8,1 years (n=160): in the group of patients without frailty — 72,4±6,9 years (n=50), with prefrailty — 76,6±8,1 years (n=50), with frailty — 81,7±6,6 (n=60). Patients with frailty had a higher CAVI than those without frailty and with prefrailty (10,3±1,6 vs 9,3±1,0 and 9,6±1,8, respectively; p=0,002).In patients with frailty, a negative correlation was found between the vascular stiffness and body mass index (BMI) (Rs=-0,392 (p=0,002)), and a positive correlation between the CAVI and orthostatic response (Rs=0,382 (p=0,003). In patients with prefrailty, negative relationships were found with the dynamometric parameters (Rs=-0,329 (p=0,019)), BMI (Rs=-0,343 (p=0,015) and physical activity (Rs=-0,285 (p=0,047)).In patients without frailty, the vascular stiffness was associated with an increased total cholesterol level (Rs=0,379 (p=0,009)), a low physical activity (Rs=-0,355 (p=0,015)), as well as negative correlations were found with the clock-drawing test and falls (Rs=-0,458 (p=0,011) and Rs=-0,306 (p=0,031), respectively).Conclusion. Vascular stiffness in elderly patients with frailty is associated with a decrease in body mass index and orthostatic hypotension. At the stage of prefrailty, the relationship between the vascular stiffness and muscle strength decrease (according to dynamometry) was revealed.Thus, the vascular stiffness is associated with frailty markers itself

Cardiovascular disease in rural Kuzbass aborigines - teleut

The study is focused on cardiovascular disease and mortality dynamics in teleuts, living in a specific Western Siberia region (Kuzbass), situated in ecologically adverse intra-mountain basin with very high urbanization level. The rural teleut population represents one of so called small nations. The study (2005-2006) demonstrated arterial hypertension prevalence and 35-year mortality dynamics in teleut population

(1<i>R</i>,2<i>R</i>,4<i>R</i>)-<i>N</i>-((4-((4-(2-Carboxyethyl)phenoxy)methyl)thiophen-2-yl)methyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-aminium Chloride

A novel free fatty acid receptor 1 (FFAR1) agonist has been synthesized and evaluated in vitro. The synthesis of the title compound was performed from commercially available 4-hydroxybenzaldehyde, 2-thiophenecarboxaldehyde, and (+)-camphor. The compound was shown to have an affinity to FFAR1

Synthesis and Evaluation of Hypoglycemic Activity of Structural Isomers of ((Benzyloxy)phenyl)propanoic Acid Bearing an Aminobornyl Moiety

Free fatty acid receptor-1 (FFAR1) agonists are promising candidates for therapy of type 2 diabetes because of their ability to normalize blood sugar levels during hyperglycemia without the risk of hypoglycemia. Previously, we synthesized compound QS-528, a FFA1 receptor agonist with a hypoglycemic effect in C57BL/6NCrl mice. In the present work, structural analogs of QS-528 based on (hydroxyphenyl)propanoic acid bearing a bornyl fragment in its structure were synthesized. The seven novel compounds synthesized were structural isomers of compound QS-528, varying the positions of the substituents in the aromatic fragments as well as the configuration of the asymmetric center in the bornyl moiety. The studied compounds were shown to have the ability to activate FFAR1 at a concentration of 10 μM. The cytotoxicity of the compounds as well as their effect on glucose uptake in HepG2 cells were studied. The synthesized compounds were found to increase glucose uptake by cells and have no cytotoxic effect. Two compounds, based on the meta-substituted phenylpropanoic acid, 3-(3-(4-(((1R,2R,4R)-1,7,7-trimethylbicyclo-[2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid and 3-(3-(3-(((1R,2R,4R)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid, were shown to have a pronounced hypoglycemic effect in the oral glucose tolerance test with CD-1 mice