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Development trends need the necessity for wider use of the local resources and available natural materials are one of the priorities around the world. Freshwater sapropel is a common material in the water basement of the lakes, but still not sufficiently explored. The main goal of the project to start detailed and systematic research on the medical properties of sapropel to be obtained in Latvia, promote its scientifically based use in balneology, develop new medical procedures and services, and promote development of new exportable products. The results include the survey, sampling depths, and processing, evaluation of external signs, physical, chemical, and biochemical parameters, and evaluation of microbiological indicators. Active components from the sapropel samples extracted using the alkaline method. Sapropel extracts were characterized by organic carbon content, humic and fulvic acid concentrations, total phenolic content, trace metal and pesticide concentrations, total antioxidant status, and microbiological flora. Summarizing the article's main findings it was concluded that Latvian freshwater sapropel can be used as raw material for obtaining sapropel extract and use it in the preparation of pharmaceuticals and promote the development of new exportable products and services.

Doctoral Thesis has been worked at: Rīga Stradiņs University Laboratory of Biochemistry, in collaboration with Biomedical Research Centre of Sheffield Hallam University and Randox Laboratories, Ltd, United Kingdom; the Centre of Occupational and Radiological Medicine of Pauls Stradins Clinical University Hospital; Endocrinology Clinic, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania. Defence: on April 20, 2015, at 15.00 at an open meeting of Doctoral Council of Medicine of Rīga Stradiņs University, in the Lecture theatre Hippocrates, 16 Dzirciema Street, Riga.

Background Development trends need the necessity for wider use of the local resources and available natural materials are one of the priorities around the world. Freshwater sapropel is a common material in the water basement of the lakes in Latvia, but still not sufficiently explored. The main goal of the project to start detailed and systematic research on the medical properties of sapropel to be obtained in Latvia, promote its scientifically based use in balneology, develop new medical procedures and services, and promote development of new exportable products. Results The results include the survey, sampling depths and processing, evaluation of external signs, physical, chemical and biochemical parameters and evaluation of microbiological indicators. Active components from the sapropel samples extracted using the alkaline method. Sapropel extracts were characterized by organic carbon content, humic and fulvic acid concentrations, total phenolic content, trace metal and pesticide concentrations, total antioxidant status and microbiological flora. Conclusions Summarizing the article's main findings it was concluded that Latvian freshwater sapropel can be used as raw material for obtaining sapropel extract and use it in the preparation of pharmaceuticals and promote the development of new exportable products and services.

Sapropel has been used for different purposes - in agriculture as fertilizer, in construction as building material, in cosmetic products, in balneology also in medicine and pharmaceuticals as bioactive component. Previously sapropel has been commonly used in raw form and there is no general accepted method or standard method for obtaining sapropel extract. However, most extraction methods follow the same path. Currently, there are few extraction methods using several extractants for obtaining bioactive components from raw sapropel. The most commonly used extractant is alkaline solution. When sapropel is subjected to alkaline environment, the humic and fulvic acids, together with some lipids, vitamins and sugar, present in the raw sapropel become soluble, however other organic and mineral content present in the sapropel remain solid. Alkaline extraction is followed by filtration and water present in the aqueous mixture is evaporated off. Latvian freshwater sapropel can be used as raw material for obtaining sapropel extract and use it as remedy. But the main question for sapropel usage in medicine, balneology and pharmacy is to develop quality criteria for raw sapropel and its extracts. The quality criteria should include minimum requirements for biologically active substance concentration, pH values, antioxidants as well as physical characteristics. In future studies the differences in extract characteristics of the various deposit sites, as well as the stability of the extracts under different storage conditions should be defined; also, there is need for a common approach to develop method of extraction process for active substances from sapropel and analysis procedures of its extract.

Glutathione, in its thiol-reduced form (GSH), is the most abundant antioxidant in the airway epithelial lining fluid. It acts as a vital intra- and extracellular antioxidant protecting oxidative/nitrosative stress, interceding the pro-inflammatory processes in the lungs. Aim: Relationship between pneumonia severity and GSH level have been studied. Methods: A case-conrol study took place at P. Stradins Clinical University hospital, Riga, Latvia. Community-acquired pneumonia (CAP) patients with no underlying chronic heart failure (n=32), both males and females of average age 69,0+7,2 and healthy control patients matched for age (n=20) were recruited. CURB 65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) score was used for CAP severity assessment. The level of plasma GSH was determined. CAP clinical pattern was followed up for 3 weeks. Results: Being compared to control group, GSH level was reduced in CAP patients (mean GSH was 1.12+ 0,22 mmol/L versus 1.60+0,16 mmol/L accordingly). There was no correlation between GSH level and CAP severity by CURB65. However, in 8 patients respiratory failure (RF) has developed. All the patients, in whom RF has developed, demonstrated GSH level below 1,1 mmol/L on admission. Conclusions: A low concentration of plasma GSH indicating low antioxidant capacity could act as a marker for inflammation-related OS in CAP patients for its management and/or risk of complications stratification.

Acute respiratory distress syndrome (ARDS) is common and multi factorial, clinically described as an inflammatory lung disorder that is associated with major morbidity and high mortality in intensive care patients. Recently, investigators have revised the AECC criteria from 1994. To diagnose ARDS and discover its severity we presently use Berlin definition criteria. An important role in developing of ARDS may be through a disbalance between reactive oxygen species (ROS), which have both oxidant and antioxidant compartments. The pathogenesis of ARDS is very complex, and unfortunately, the dynamic development of ARDS in an individual patient is difficult to recognise. ROS can initiate cellular tissue damage by modifying lipids, proteins and DNA, which can seriously compromise cell life ability or induce a large number of cellular responses through generation of secondary reactive species, leading, at last, to cell death by necrosis or apoptosis. Studies have shown that many patients with organ malfunction at admission to the intensive care units (ICU) show decreased antioxidative properties, worsening the harmful effects of lipid peroxidation. That is the reason why predicting development of ARDS has great value for intensive care specialists.

Introduction. Patients in the intensive care unit (ICU) are likely to suffer from acute respiratory failure (ARF) with a risk of developing acute lung injury (ALI) and its more severe condition, acute respiratory distress syndrome (ARDS) with 30 - 50% mortality. Evidence shows, that important role in ARDS pathophysiology may play an imbalance between oxidant and antioxidant species. Oxidative stress is well established in adult critical illnesses characterized by systemic inflammatory response. Aim of the study was to investigate the influence of oxidative stress species on developing of acute respiratory distress syndrome in patients at risk. Materials and methods. The study was conducted in Pauls Stradins Clinical University Hospital ICU during 6 months in 2013 and approved by ethics committee. There were included 15 ARDS risk patients over 18 years of age with mechanical lung ventilation (MLV) over 24 hours and massive blood component transfusions, acute severe pancreatitis, pneumonia or sepsis. Blood samples were taken three times during observational period- first sample were taken just exactly after inclusion, second sample- on 4th and the last sample- on 7th day after inclusion. The developing of ARDS were diagnosed using revised diagnostic criteria according to the Berlin definition. Reactive oxygen species were measured in plasma using manual or automatic spectrophotometry. Results. Among included patients 82.4 % were males with the mean age 49.3 years, for female 67 years. The most popular diagnosis was acute severe pneumonia (n= 5; 33.3 %), followed by patients with sepsis (n= 4; 26.7%) and acute severe pancreatitis (n= 4; 26.7%). The most informative marker of oxidative stress among all ARDS risk patients is GPx, which correlates with PaO2/ FiO2 and oxidation index (R= -0.52; p= 0.045 and R= 0.57; p= 0.027) at the 1st day of observation. At the 4th day of observation GPx shows statistically significant relation with the level of PEEP (R= 0.57; p= 0.033). Among ARDS patients we have found correlation between PaO2/FiO2 ratio and MDA+ HNE plasma levels (R= 0.69; p= 0.026) at the 1st day of observation. Conclusion. Reactive oxygen substances causing oxidative stress shows a dynamic changes in ARDS patients. The changes of some oxidative markers are related to the increased level of hypoxemia and PEEP used in treatment of ARDS patients.

Increased excitotoxity in response to stressors leads to oxidative stress (OS) due to accumulation of excess reactive oxygen/nitrogen species. Neuronal membrane phospholipids are especially susceptible to oxidative damage, which alters signal transduction mechanisms. The Contingent of International Operations (CIO) has been subjected to various extreme stressors that could cause Posttraumatic Stress Disorder (PTSD). Former studies suggest that heterogeneity due to gender, race, age, nutritional condition and variable deployment factors and stressors produce challenges in studying these processes. The research aim was to assess OS levels in the PTSD risk group in CIO. In a prospective study, 143 participants who were Latvian CIO, regular personnel, males, Europeans, average age of 27.4, with the same tasks during the mission, were examined two months before and immediately after a six-month Peace Support Mission (PSM) in Afghanistan. PCL-M questionnaire, valid Latvian language “Military” version was used for PTSD evaluation. Glutathione peroxidase (GPx), superoxide dismutase (SOD) and lipid peroxidation intensity and malondialdehyde (MDA) as OS indicators in blood were determined. Data were processed using SPSS 20.0. The MDA baseline was 2.5582 μM, which after PSM increased by 24.36% (3.1815 μM). The GPx baseline was 8061.98 U/L, which after PSM decreased by 9.35% (7308.31 U/L). The SOD baseline was 1449.20 U/gHB, which after PSM increased by 2.89% (1491.03 U/gHB). The PTSD symptom severity (total PCL-M score) baseline was 22.90 points, which after PSM increased by 14.45% (26.21 points). The PTSD Prevalence rate (PR) baseline was 0.0357, which after PSM increased by 147.06% (0.0882). We conclude that there is positive correlation between increase of OS, PTSD symptoms severity level, and PTSD PR in a group of patients with risk of PTSD - CIO. PTSD PR depends on MDA intensity and OS severity. OS and increased free radical level beyond excitotoxity, is a possible causal factor for clinical manifestation of PTSD

Acute respiratory distress syndrome is a common complication characterised by severe hypoxemia, which leads to high mortality rates in ICU patients. Imbalance between oxidative stress markers like oxidants and antioxidants may play an important role in pathophysiology of the syndrome. We observed 17 ARDS patients during seven days after inclusion, with the main goal to describe dynamic changes in the level of oxidative stress markers in patients with acute respiratory distress syndrome. We found that there are dynamic differences in the level of malondialdechyde (MDA) and nitric oxide (NO) in patients with acute respiratory distress syndrome. There were also different levels of oxidative stress markers in non-survivor compared with survivor groups. Increased level of an oxidant like a thiobarbituric acid substance with malondialdechyde (TBS_MDA) and antioxidant glutathionperoxidase (GPx) at the first day after inclusion was related with poor outcome in patients with acute respiratory distress syndrome.

To establish if there is further evidence for the long-term oxidant stress injury (as reported previously--Kumerova et al. in Biol Trace Elem Res 77:1-12, 2000) in surviving Chernobyl nuclear power plant (NPP) workers from Latvia. The overall objectives of this study have been to establish if there have been long-term systemic changes in the oxidant/antioxidant status of clean-up workers that might reflect adaptation to the progression of oxidative stress injury.Biochemical analyses of the circulating levels of endogenous oxidants and anti-oxidants were undertaken over two periods (Stage 1 in 1998-1999 and Stage 2 in 2005-2006) at approximately 6-7 years time interval, in order to establish if there have been time-dependent changes in the parameters that may be important for the health of the clean-up workers. The biochemical analyses included (a) plasma levels of the anti-oxidant, selenium, (b) blood and plasma levels of glutathione peroxidase, (c) red blood cell catalase, (d) plasma total oxidant status as lipid peroxides and hydroperoxides, (e) plasma ceruloplasmin, and (f) total blood levels of zinc and copper.The circulating content of lipid peroxides, plasma oxidisability, lipid peroxides, catalase, Zn, and Cu were elevated above normal values at both the stages of this study. Glutathione peroxidase was increased above normal values at Stage 1 but not at Stage 2. The most pronounced changes between Stage 1 and Stage 2 were (a) a reduction by about (1/2) in the content of lipid peroxides and lipid peroxidation, but not in the blood oxidisability and (b) increased plasma selenium. The data show that there may be a partial improvement in the anti-oxidant/oxidant status of the Chernobyl NPP workers over the 7-year period of investigation.The NPP patients may be undergoing progressive reduction in blood oxidants accompanied by adaptation to oxidant stress injury due to the increased anti-oxidant activity measured in their plasma and blood.

Interest in finding natural antioxidants for use in food or medical materials to prevent free radical imbalance has increased considerably over the past years. The aim of this research was to evaluate changes in glycemic control and psychological state of patients with type 2 diabetes mellitus (T2DM) after use of antioxidant plant preparations. Fifty-six patients with T2DM were randomly allocated to receive standardized Ginkgo biloba L. leaves dry extract, green tea dry extract, or placebo capsules. Diabetes glycemic control measured as glycated hemoglobin (HbA1c) level, antioxidant state and psychological data were evaluated at baseline, after 9 and 18 months of using either antioxidant preparations or placebo. The level of perceived stress lowered significantly after 9 months (p = 0.038) and 18 months (p = 0.030), and the psychological aspect of quality of life significantly improved after 18 months (p = 0.019) of use of G. biloba extrac. No significant differences were detected after using green tea extract. In patients using placebo, significant lowering of HbA1c level was observed after 18 months (p = 0.017). In conclusion, antioxidant G. biloba leaf extract exhibited a mild effect on psychological state and a trend of improving glycemic control in patients with type 2 diabetes mellitus.

More than 40 volatile compounds with pharmacological effects (including antioxidant, anti-inflammatory, anticancer, radioprotective activity and improvement of cardiovascular risk factors, etc) are detected in the sea buckthorn. The most thoroughly investigated parts of sea buckthorn are berries – their juice and oil, but less is known about the bioactives of the other plant parts. This study aims to determine antioxidative (AO) and antiradical (AR) properties of sea buckthorn sprouts. The study results show differences between spring and autumn sprouts’ collection as well as water and 70% ethanol extracts. Further, in vivo research needs to be done to provide a full understanding of sea buckthorn sprouts’ AO and AR effects.

The prevalence of diabetes mellitus (DM) has dramatically increased in the past decade. Furthermore, increasing evidence from research shows that oxidative stress (OS) plays a crucial role in the pathogenesis of diabetes and in its complications. A search for ways to reduce oxidative damage has become the focus of interest for the majority of scientists. In this study, we determined the radical scavenging activity of single green tea constituents by using an on-line high performance liquid chromatography (HPLC)–2,2-diphenyl-1-picrylhydrazyl (DPPH) method and evaluated the antioxidant effects on type 2 diabetic patients by performing a double-blind, placebo-controlled study. Epigallocatechin gallate was identified as the most potent antioxidant, contributing approximately 50% of the total antioxidant capacity of green tea extract. We also found a statistically significant decrement of lipid peroxidation markers in patients treated with green tea extract after 9 months or after 18 months of follow-up. Overall, these findings are attractive for diabetic patients, helping them to keep a high level of performance and well-being, which ultimately may delay the time of disability and reduce mortality.

Interest in finding natural antioxidants for use in food or medical materials to prevent free radical imbalance has increased considerably over the past years. The aim of this research was to evaluate changes in glycemic control and psychological state of patients with type 2 diabetes mellitus (T2DM) after use of antioxidant plant preparations. Fifty-six patients with T2DM were randomly allocated to receive standardized Ginkgo biloba L. leaves dry extract, green tea dry extract, or placebo capsules. Diabetes glycemic control measured as glycated hemoglobin (HbA1c) level, antioxidant state and psychological data were evaluated at baseline, after 9 and 18 months of using either antioxidant preparations or placebo. The level of perceived stress lowered significantly after 9 months ( p=0.038) and 18 months ( p=0.030), and the psychological aspect of quality of life significantly improved after 18 months ( p=0.019) of use of G. biloba extract. No significant differences were detected after using green tea extract. In patients using placebo, significant lowering of HbA1c level was observed after 18 months ( p=0.017). In conclusion, antioxidant G. biloba leaf extract exhibited a mild effect on psychological state and a trend of improving glycemic control in patients with type 2 diabetes mellitus.

Objectives: Diabetes mellitus has been one of the most crippling diseases that man has seen, and its prevalence has risen dramatically over the past two decades. Currently, there are over 150 million diabetics worldwide and this number is likely to increase to 300 million or more by the year 2025. Diabetes mellitus increases the risk of many disorders including cardiovascular diseases. Understanding the molecular properties of diabetic progression is a big challenge in the system biology era. The aim of this study is to determine association in albumin modifications between Chernobyl clean-up workers with and without type 2 diabetes mellitus. Methods: ABM (3-aminobenzanthrone derivative developed in Daugavpils University, Latvia) has been previously shown as a potential biomarker for determination of the immune state of patients with different pathologies. In this study several aspects of plasma albumin alterations in the group of Chernobyl clean-up workers with diabetes mellitus in relation to the group of workers without diabetes mellitus and people having no professional contact with radioactivity were determined. The following parameters were examined: (1) spectral characteristics of ABM in blood plasma; (2) effective and total albumin concentration in blood plasma; and (3) quantitative parameters of albumin auto-fluorescence. Results: Screening of individuals with diabetes mellitus 25-26 years after their work in Chernobyl revealed two groups of patients differing in structural and functional properties of membrane. The revealed structural modifications of membrane are dependent on radiation-induced factors. Concomitant diseases (diabetes mellitus, cardiovascular diseases) reinforce radiation-induced effects. Conclusion: ABM is a sensitive probe of albumin alterations; it can be used to elucidate the changes in protein systems. Significant differences in albumin dynamics exist between the control group (donors) and that of diabetics and non-diabetics in the Chernobyl clean-up workers.

Objectives: Albumin is one of the most generously represented proteins in human blood plasma. Therefore it is important to follow and assess the transport function of albumin in clinic researches. Disturbances in structural/functional properties of albumin play an important role in the pathogenesis of various diseases (e.g. diabetes mellitus). Changes in albumin transformation can serve as a diagnostic and prognostic criterion in pathologies. The aim of this study was to determine and compare several aspects of plasma albumin alterations in patients with diabetes mellitus and the group of Chernobyl clean-up workers with diabetes mellitus as the main concomitant disease. Methods: ABM (3-aminobenzanthrone derivative developed at Daugavpils University, Latvia) has been previously shown as a potential biomarker for determination of the immune state of patients with different pathologies. The following parameters were examined: (1) the spectral characteristics of ABM in blood plasma; (2) “effective” (EA) and total albumin (TA) concentration in blood plasma; (3) quantitative parameters of albumin auto-fluorescence, characterizing the tryptophanyl region of molecule and advanced glycation end products (AGEs). Results: Qualitatively different albumin modifications were obtained in diabetics and Chernobyl clean-up workers. The different modifications of albumin are associated with different binding sites for the probe, differing in affinity, quantum yield, and degrees of polarization. Rigidity (dehydration) of the tryptophanyl region is more expressed in Chernobyl clean-up workers group with diabetes mellitus as compared to the other diabetics. Concomitant diseases (e.g. diabetes mellitus) reinforce radiation-induced effects. Conclusion: ABM is a sensitive probe of albumin alterations and can be used to elucidate the changes in protein systems. Significant differences in albumin dynamics exist between diabetics and a group of Chernobyl clean-up workers with diabetes mellitus as the main concomitant disease.

Objective: Diabetes mellitus is one of the most crippling diseases that man has seen and its prevalence has risen dramatically over the past two decades. Currently there are over the 150 million diabetics worldwide and this number is likely to increase to 300 million or more by the year 2025. Diabetes mellitus increases the risk of many disorders including cardiovascular diseases. Understanding the molecular properties of diabetic progression is a big challenge in systems-biology era. Methods: The 3-aminobenzanthrone derivative ABM, developed at the Daugavpils University, Latvia, has been previously shown as a potential biomarker for determination of the immune state of patients with different pathologies. The aim of this study was to determine the several aspects of membrane alterations in the group of Chernobyl clean-up workers with diabetes mellitus in relation with its common group without diabetes mellitus and humans having no professional contact with radioactivity. The following parameters were examined: (1) the spectral characteristics of ABM in cell suspension (e.g. anisotropy index); (2) quantitative parameters of protein/lipid interaction in liposomes prepared from phosphatidylcholine and its mixtures with cardiolipin and cholesterol. Results: Screening of the individuals with diabetes mellitus 25-26 years after the work in Chernobyl revealed two groups of patients differing in structural and functional membrane properties, first of all on the lipid/protein interrelations and conformations of membrane proteins. The revealed structural modifications of membranes are dependent on radiation-induced factors. Concomitant diseases (diabetes mellitus, cardiovascular diseases) reinforce radiation induced effects. Conclusion: ABM is a sensitive probe of membrane architecture alterations, and can be used to elucidate the changes in membrane systems. Significant differences in membrane dynamics exist between control (donors), and diabetics and non-diabetics groups of Chernobyl clean-up workers

This paper describes the effects of prolonged antioxidant therapy, its stability and association with spectral parameters of the fluorescent probe ABM in blood plasma and indices of albumin auto-fluorescence in Chernobyl clean-up workers from Latvia. Patients were divided into two groups. Group 1 received placebos of identical appearance to antioxidants. Group 2 received antioxidants (vitamin E + selenium + ibuprofen). Individuals were tested three times: before supplementation of antioxidants, after therapy and one year after supplementation interruption. Applied therapy improves oxidant/antioxidant status of individuals. Interruption of therapy after one year leads to significant decrease of cellular immunity. In the group receiving antioxidants it is not so expressed compared with data from the placebos group. Changes in blood plasma and its structural and functional properties detected by ABM strongly correlated with the oxidant/antioxidant (immune) status of individuals. This behaviour of ABM could be useful in reflecting alterations of cellular immunity. Questions related to more detailed and prolonged antioxidant therapy need closer investigation.