Experience of using mineral waters in patients with type 1 diabetes mellitus for the correction of endotoxinemia

Aim. To evaluate the effect of grape polyphenol concentrate on the state of lipopolysaccharide-binding systems, lipid profile, levels of circulating lipopolysaccharide (LPS) and markers of inflammation in patients with type 1 diabetes mellitus. Design. Analytical comparative mixed sample controlled retrospective pilot study. Materials and methods. The study included 58 patients with a verified diagnosis of type 1 diabetes mellitus. Participants in the intervention group (n = 30), in addition to basic bolus insulin therapy, received grape polyphenol concentrate 1 teaspoon per day with meals for 4 weeks. However, during the study, 4 patients had side effects associated with taking polyphenol concentrate, which caused them to be excluded from the experiment. In this regard, data from 26 patients of the 1st group will be presented. The control group consisted of 28 patients with a verified diagnosis of type 1 diabetes mellitus, who were comparable in gender and age to patients in the experimental group. In the patients of the experimental group, before and after the application of grape polyphenol concentrate, and in the participants of the control group, 30 days after the start of the study, biological material (blood plasma) was taken for further enzyme immunoassay (ELISA). ELISA kits manufactured by Cloud-Clone Corp. were used to determine the levels of C-reactive protein (CRP), interleukin 6, zonulin, LPS, lipopolysaccharide-binding protein (LBP), and low-density lipoproteins (LDL), including apolipoprotein B-100 (apoB-100). Results. Statistically significant decreases in CRP levels were recorded in the intervention group (from 2.73 (2.32–3.09) to 2.13 (0.94–2.39) mg/l, p = 0.002), LDL (from 3.4 (2.2–5.89) to 2.32 (1.87–2.83) mmol/L, p = 0.028) and apoB-100 (from 2.65 (2.35–2.8) to 2.29 (2.1–2.6) g/l, p = 0.023), an increase in the content of LBP (from 6.1 (5.45–8.62) to 9.18 (8.2–13.19) mg/l, p = 0.002). No significant changes were detected in the control group. Conclusions. A 30-day course of grape polyphenol concentrate in addition to insulin therapy in patients with type 1 diabetes mellitus gives significant positive effects — a decrease in systemic inflammation (in terms of CRP) and an improvement in the lipid profile (a decrease in LDL and apoB-100 concentrations). An increase in the level of LBP indicates the activation of bacterial endotoxin binding and detoxification systems, although a significant decrease in the level of circulating LPS was not achieved in a short period of observation. Keywords: type 1 diabetes mellitus, polyphenols, endotoxin, lipopolysaccharide, inflammation, lipid profile

This article considers the distribution, formation, and chemical composition of mineral waters of the Eastern region of Ukraine, and, in particular, Donetsk, Luhansk, and Kharkiv regions. The main types of mineral waters, most characteristic of the Eastern region of Ukraine, are determined. Their formation and distribution are considered. Manifestations of ferrous, bromine, boron and iodine waters have been studied in this region, which significantly expands hydromineral and balneological resources. The application of ferrous mineral waters to organisms exposed to radiation has been studied. Since one of the consequences of radiation damage is a violation of oxidative homeostasis, the effect of ferrous mineral waters on the course of free radical processes in the body was studied. The peculiarities of the organic composition and biological properties of Berezivsky mineral waters have been studied to identify them as Naftusya-type waters. It is established that Berezivsky mineral waters do not have a pronounced radiomodifier effect. They are inhibitors of the enzymatic activity of catalase — a key regulator of oxidative metabolism, which leads to a deterioration in the vital functions of the body after irradiation. According to the obtained data of mass spectra, active organic substances of different classes, which are part of mineral waters of the Naftusya type, differ from organic substances of Berezivsky mineral waters, both qualitatively and quantitatively. Therefore, Berezivsky mineral waters cannot be referred to as the class of mineral waters of the Naftusya type. Some studies were also conducted and an array of statistics was obtained, which showed that the mineral waters of the Podilsk region, Naftusya and Berezivsky waters have pesticide concentrations less than 0.01 ng/dm3, i.e. 10 000 times lower than their permissible concentrations according to international standards. This confirms the possibility of widespread use and export of Ukrainian mineral waters, which is of national importance. Prospects for the development and use of mineral waters in the Eastern region are shown.

Aim. Evaluation of markers of systemic inflammation in patients with chronic heart failure in comorbidity with chronic kidney disease.Methods. The study included 188 patients with heart failure and kidney disease including control group (76 patients) with heart failure with preserved renal function aged 38 to 83 years (mean age 66.8±10.1 years), with the duration of heart failure of about 8 years. Quantitative measurement of C-reactive protein and proteins of blood serum and daily excretion of protein with urine were performed.Results. Glomerular filtration rate in patients without renal pathology was 71.1±11.7 ml/min/1.73 m2, and in the group with heart failure associated with kidney dysfunction it was 51.5±19.1 ml/min/1.73 m2. C-reactive protein, γ-globulin, albumin and total serum protein in patients with chronic kidney disease differed from those in patients with heart failure without kidney damage.Conclusion. C-reactive protein and γ-globulin in the serum significantly increase in patients with heart failure and chronic kidney disease and can be used as markers of cardiac as well as renal events.

Calcul coralliforme du nourrisson lié à la prise exclusive d’eau minérale riche en calcium

The great German composer of the First Viennese School Ludwig van Beethoven suffered from hearing impairment and diseases of the digestive system for most of his life. His health status strongly influenced both his life and creativity. The use of mineral waters in the first half of the 19th century was an important part of the therapeutic arsenal of physicians; it was actively used in the Beethoven’s treatment. Balneotherapy is one of the least‑studied aspects of the composer’s medical history. The purpose of the research was to study the use of mineral water in the treatment of Ludwig van Beethoven. Beethoven’s letters and works of his most authoritative biographers were analyzed with a view to revealing information about the use of mineral waters in his treatment. Scopus, WebOfScience, MedLine and PubMed databases, electronic archives were searched without time restriction for information on the use of mineral waters in European spa resorts in the first half of the 19th century. Since 1796, Beethoven suffered chronic enterocolitis and progressive hearing impairment, since 1820 — portal cirrhosis of the liver. Mineral water intake was an important part of Beethoven’s treatment from 1799 until his death in 1827. The medicine of its time was mainly empirical, the diagnosis was based only on the data of a survey and examination of the patient, methods of physical research have not yet received wide application. Beethoven’s treatment meets the advanced achievements of balneology at the end of the 18th century. The composer annually took mineral water at spa resorts (Baden, Teplice, Carlsbad, Franzenbrunn) during the season (up to 6 months) and continued to receive bottled mineral water in Vienna. Spa therapy (and, in particular, mineral water intake) became part of Ludwig van Beethoven’s life.

The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired clearance of gut-derived neurotoxins and increased systemic inflammation are thought to play key roles. The diagnosis is based on detection of neurophysiological and neuropsychometric abnormalities. The Psychometric Hepatic Encephalopathy Score (PHES) have been found to correlate with markers of systematic inflammation including interleukin 6, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). This study explores the associations between the PHES score and systemic inflammation, endotoxins and disease severity using baseline data from a trial involving patients with cirrhosis and minimal or no HE (NCT01769040). Arterial blood was obtained during hepatic vein catheterization, from 54 patients [median age 55 (range, 33-70) years; 83% men] with decompensated but stable cirrhosis. None had clinical evidence of HE but 34 (55.6%) had an abnormal PHES score indicating the presence of minimal HE. Relationships were sought between the PHES score and markers of systemic inflammation, high sensitivity-CRP, cytokines (SDF-1α, TGF-b1, IP-10, IL-6, 10 and 18, and TNF-α; lipopolysaccharide (LPS), the lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14); and the blood ammonia. No significant relationships were found between the PHES score and any of the variables tested with the single exception of the correlation with serum IL-6 (r=-0.29, 95% confidence interval, -0.53 to -0.02, P=0.031). No independent predictors of the PHES score were identified in regression analyses. No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.

This study was designed to determine the effect of exenatide on inflammatory and oxidative stress markers in type 2 diabetes mellitus (T2DM) patients who were suboptimally controlled with metformin and/or sulfonylurea. Twenty-three patients with T2DM with inadequate glucose control were randomly divided into two groups: exenatide group (E group) (12 patients, 5 μg b.d. × 4 weeks followed by 10 μg b.d. × 12 weeks) and placebo group (P group) (11 patients). Glycosylated hemoglobin (HbA1c), the seven-point glucose profile, daily mean glucose, and glycemic excursion were determined. The effects of exenatide on 8-iso-prostaglandin F2α (PGF2α), monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP) were investigated. Exenatide treatment reduced body weight and body mass index (BMI) and improved HbA1c, the seven-point glucose profile, and daily mean glucose compared with placebo (P < 0.05). Limited glycemic excursion was found in the E group compared with the P group (P < 0.05), including a smaller SD and postprandial glucose excursion. In addition, the oxidative stress maker PGF2α was significantly reduced by exenatide treatment (P < 0.05). The inflammatory markers hs-CRP and MCP-1 were also significantly reduced in the E group compared with the P group (P < 0.05). PGF2α was significantly correlated with glycemic excursion (P < 0.05), whereas MCP-1 was significantly correlated with body weight, BMI, glycemic excursion, and HbA1c (P < 0.05 for all). Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

Background: A low serum 25-hydroxyvitamin D (25(OH) D) concentration has been associated with a higher risk of type 2 diabetes mellitus (T2DM), especially in older people. Our aim in this randomized controlled trial was to evaluate the effect of vitamin D treatment on inflammatory markers in non-obese Lebanese patients with T2DM, living in Beirut, Lebanon. Methods: Non-Obese patients with T2DM (n = 88), deficient/insufficient in vitamin D, were randomly assigned into one of two groups—a treatment group receiving 30,000 IU cholecalciferol/week for a period of six months, and a placebo group. Serum concentrations of TNF-α, high-sensitivity C-reactive protein (hs-CRP), and Interleukin-6 (IL-6) were the primary outcomes. A homeostatic model of insulin resistance (HOMA-IR) was assessed, in addition to serum concentrations of fasting blood glucose (FBG), HbA1C, (25(OH) D), and PTH. Results: The vitamin D group showed higher blood levels of (25(OH) D) (p < 0.0001), and a significant reduction in hs-CRP and TNF-α concentrations (p < 0.0001) compared to placebo. The decrease perceived in IL-6 concentrations was not significant (p = 0.1). No significant changes were seen in FBG (p = 0.9) and HbA1c levels (p = 0.85). Conclusion: Six months of vitamin D supplementation led to a decrease in some inflammatory markers in patients with T2DM. Additional studies with a larger sample and a longer period are advised in this regard. This trial was registered at ClinicalTrial.gov; Identifier number: NCT 03782805.

Objective: the aim of the study was to investigate laboratory markers of inflammation in patients with stable ischemic heart disease, to estimate their interrelation with symptoms of depression. Matherials and methods: 46 men aged from 46 to 75 years hospitalized for the conservative (n = 20) and surgical (n = 26) treatment of ischemic heart disease participated in the study. An evaluation of inflammatory markers (absolute quantity of leukocytes and neutrophils, monocyte/HDL ratio and neutrophil/lymphocyte ratio) was performed. Depressive symptoms were measured using the CES-D scale. Conclusions: symptoms of depression were found in 8 patients (17,37%). 13% of them had symptoms of mild depression, 4,37% - symptoms of severe depression. The monocyte/HDL ratio was significantly higher in patients with ischemic heart disease comparing to healthy individuals. The monocyte/HDL ratio was significantly increased in patients with depressive symptoms, previously implanted stent, restenosis of the coronary stent in anamnesis. Level of leukocytes was higher during the early period after the procedure of percutaneous coronary intervention with stenting and in patients with stent restenosis. Number of neutrophils and the neutrophil/lymphocyte ratio were significantly higher in patients with depression symptoms, during the early period after stent implantation and also with previous restenosis of the stent. Systemic inflammation estimated using routine laboratory tests was significantly higher in both patients with complicated ischemic heart disease, and with symptoms of depressive disorder. Routine laboratory indicators can be informative in assessing inflammation in patients with ischemic heart disease. Symptoms of depression and stent restenosis can be followed by increased inflammatory markers.

Introduction. Metabolic syndrome (MS) is considered a combination of several pathological processes – obesity, high blood pressure, dyslipidemia, carbohydrate metabolism disorder, and diabetes mellitus (DM), which determines the involvement of many functional systems of the body. One method for correcting metabolic disorders is crenotherapy, i.e., drinking various mineral waters (MW). The research aims to determine experimentally the possibility of using MW with a high content of organic substances to restore the morpho-functional parameters of the body of a rat with a model of metabolic syndrome. Materials and methods. Twenty-four rats were reproduced in the MS model using a high-glycemic load diet. After reaching the MS model, all rats were randomly divided into two groups of 12 animals each. All rats continued to receive the diet described above; however, the second (experimental) group also received intragastric MW with a high content of organic substances at a dose of 1% of body weight. Results. The establishment of the MS model in rats is a crucial step, as it leads to significant functional disorders of the liver and kidneys. A comprehensive study of the histological structure of the liver and kidneys in rats with a model of MS revealed the dystrophic changes in hepatocytes and nephrons, underscoring the relevance of our research. MW treatment significantly improved the structural characteristics of the liver and kidney parenchyma of experiment rats. The level of endogenous intoxication normalized, and the water-electrolyte balance was restored. Conclusions. Using a course of MW with an increased content of organic substances in rats with a metabolic syndrome model promotes the restoration of the structural organization of liver and kidney tissue, which leads to the normalization of the corresponding functional indicators. The obtained experimental results allow us to recommend the use of mineral waters with increased organic content for clinical studies in the rehabilitation of patients with metabolic syndrome.

Water, mineral waters and health

Type 2 diabetes (T2D), as a common type of diabetes mellitus, is influenced by various factors such as genetics and environment. One of the most important risk factors for the development of T2D is insulin resistance (IR), the underlying mechanisms of which include impaired free fatty acid (FFA) metabolism and inflammation. Chronically elevated levels of plasma free fatty acids appear to disrupt normal glucose homeostasis, while increased levels of a key inflammatory marker, C-reactive protein (CRP), lead to endothelial dysfunction and other T2D complications. The aim of this study was to examine the relationship between plasma FFA concentration and CRP as an inflammatory marker in patients with diabetes. The research included 82 participants, 42 of whom were patients with type 2 diabetes and 40 healthy individuals as a control group, aged 40 to 65 years. Clinical and biochemical characteristics including body mass index (BMI), fasting glucose levels, HbA1c, insulin, CRP and lipid profile were determined using standard clinical methods, while the levels of individual FFAs were measured by gas chromatography. The results showed a positive correlation between myristic acid (C14:0) and CRP levels, as well as a negative association of docosapentaenoic acid (C22:5) with CRP levels (p&lt;0.05) in control subjects. In the group of diabetics, a negative correlation of gamma-linolenic acid (C18:3) with CRP levels was observed (p&lt;0.001). These findings suggest that concentrations of individual free fatty acids, with different chain lengths and degrees of saturation, such as C14:0 and C18:3, can be used as potential markers of low-grade inflammation and disease prognosis in T2D patients.

Modulation of Inflammatory Markers in Type 2 Diabetes Mellitus Through Gut Microbiome-Targeted Interventions: An umbrella review on meta-analyses

Background: Periodontal disease is considered as the “sixth complication of diabetes mellitus”. Patients suffering from diabetes mellitus (DM) are known to have increased susceptibility to infections which lead to poor metabolic control. Although it has been reported that improved metabolic control may lead to improved periodontal health it is still unclear whether the control of periodontal infections may improve the metabolic control of diabetes.&#x0D; Aim: To compare the effect of periodontal therapy on metabolic and inflammatory markers in diabetic patients.&#x0D; Materials and Methods: The study type was in vivo comparative study. 60 patients were selected for the study using simple random sampling method. The patients were grouped into control and case with 30 in each group. In all patients, plaque index, gingival index, probing pocket depth and clinical attachment level were assessed with the help of with The University of North Carolina probe (UNC-15) probe at baseline, 1 month and 3 month. Similarly, venous blood samples were taken for evaluating fasting glucose level, post prandial glucose level, glycated haemoglobin and C-reactive protein (CRP) at baseline, 1 month and 3 month. In treatment group, full mouth scaling and root planing was done and oral hygiene instructions was provided.&#x0D; Results: The result of the study suggested that non surgical periodontal therapy helps in controlling glycemic level and CRP values in patients with diabetes mellitus.&#x0D; Conclusion: Non-surgical periodontal treatment is associated with improved glycaemic control and reduction in CRP level in patients with DM.

ObjectivesMultiple sclerosis (MS) is an immune-mediated neurodegenerative disease of central nervous system and recent studies show that inflammatory processes are highly associated with neurodegeneration in the brain. The purpose of this study was to investigate the effect of coenzyme Q10 supplementation on inflammatory and anti-inflammatory markers in patients with MS.MethodsThis randomized, double-blind, placebo-controlled clinical study was performed among 48 patients with relapsing–remitting MS. Subjects were randomly assigned to a placebo group (n = 24) or coenzyme Q10 (CoQ10)-supplemented group (500 mg/day, n = 24). The intervention was administered for 12 weeks. Peripheral blood samples were collected at baseline and after 12-week intervention, to measure inflammatory (tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and matrix metalloproteinase (MMP)-9) and anti-inflammatory (IL-4 and TGF-β) markers.ResultsForty-five patients completed the study. After 12 weeks of intervention, the TNF-α levels (P = 0.003) decreased significantly in the CoQ10 group. Subjects in the CoQ10 group had significantly lower IL-6 levels (P = 0.037), compared to the placebo group. CoQ10 supplementation also resulted in decreased serum levels of MMP-9 as compared to the placebo group (P = 0.011). However, CoQ10 supplementation did not alter the IL-4 and TGF-β levels (P = 0.16 and P = 0.81, respectively).DiscussionCoQ10 supplementation at a dosage of 500 mg appears to decrease the inflammatory markers (TNF-α, IL-6, and MMP-9) in patients with MS.