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Tyler W LeBaron,1,2 Ram B Singh,3 Ghizal Fatima,4 Kumar Kartikey,3 Jagdish P Sharma,3 Sergej M Ostojic,5,6 Anna Gvozdjakova,7 Branislav Kura,2 Mami Noda,8 Viliam Mojto,9 Mohammad Arif Niaz,10 Jan Slezak1 1Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic; 2Molecular Hydrogen Institute, Enoch, UT, USA; 3Hospital and Research Institute, Moradabad, India; 4Era Medical College, Lucknow, India; 5Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia; 6Faculty of Health Sciences, University of Pécs, Pécs, Hungary; 7Medical Faculty, Pharmacobiochemical Laboratory of 3rd Medical Department, Comenius University Bratislava, Bratislava, Slovakia; 8Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; 9Third Internal Clinic, Faculty of Medicine, Comenius University, Bratislava, Slovakia; 10Center of Nutrition Research, International College of Nutrition, Moradabad, IndiaCorrespondence: Jan SlezakCentre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, Bratislava 841 04, Slovak RepublicTel +421 903 620 181Email jan.slezak@savba.skPurpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Pre-clinical and clinical studies have shown promising effects of H2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed.Methods: We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H2 per day) for 24 weeks.Results: Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H2 tended to promote a mild reduction in body mass index and waist-to-hip ratio.Conclusion: Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.Keywords: metabolism, fasting blood glucose, cholesterol, inflammation, oxidative stress, hydrogen water

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Diet and lifestyle choices, notably the Western-type diet, are implicated in oxidative stress and inflammation, factors that elevate the risk of cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). In contrast, the Mediterranean of diet, rich in antioxidants, appears to have protective effects against these risks. This article highlights the dual role of diet in generating molecular hydrogen ( H 2 ) in the gut, and H 2 's subsequent influence on the pathophysiology and prevention of CVD and T2DM. Dietary fiber, flavonoids, and probiotics contribute to the production of liters of H 2 in the gut, functioning as antioxidants to neutralize free radicals and dampen inflammation. In the last two decades, mounting evidence has demonstrated that both endogenously produced and exogenously administered H 2 , whether via inhalation or H 2 -rich water (HRW), have potent anti-inflammatory effects across a wide range of biochemical and pathophysiological processes. Recent studies indicate that H 2 can neutralize hydroxyl and nitrosyl radicals, acting as a cellular antioxidant, thereby reducing oxidative stress and inflammation-leading to a significant decline in CVDs and metabolic diseases. Clinical and experimental research support the therapeutic potential of H 2 interventions such as HRW in managing CVDs and metabolic diseases. However, larger studies are necessary to verify the role of H 2 therapy in the management of these chronic diseases., Competing Interests: The authors declare no conflict of interest. Jan Slezak is serving as one of the Editorial Board members of this journal. We declare that Jan Slezak had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Vincenzo Lionetti., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Recently, chronic lung diseases have been found to be associated with marked inflammation and oxidative stress, which leads to fibrosis in the lungs and chronic respiratory failure. This study aims to determine if hydrogen-rich water (HRW) can enhance oxygen saturation among patients with chronic lung diseases., Methods: Ten patients with chronic lung diseases due to COPD ( n = 7), bronchial asthma ( n = 2), and tuberculosis of the lung ( n = 1) with oxygen saturation of 90-95% were provided high-concentration (>5 mM) HRW using H 2 -producing tablets for 4 weeks. Oxygen saturation was measured via oximeter and blood pressure via digital automatic BP recorder., Results: HRW administration was associated with a significant increase in oxygen saturation (SpO 2 ) and decrease in TBARS, MDA, and diene conjugates, with an increase in vitamin E and nitrite levels, compared to baseline levels. Physical training carried out after HRW therapy appeared to increase exercise tolerance and decrease hypoxia, as well as delay the need for oxygen therapy., Conclusion: Treatment with HRW in patients with hypoxia from chronic lung diseases may decrease oxidative stress and improve oxygen saturation in some patients. HRW therapy may also provide increased exercise tolerance in patients with chronic hypoxia, but further research is needed.

Molecular hydrogen (H 2 ) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q 10 (CoQ 10 ) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H 2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H 2 ) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO 2 . The concentration of CoQ 10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ 10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H 2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ 10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H 2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H 2 therapy in patients with NAFLD.

European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR - mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16-18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q 10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome., (© 2022. The Author(s).)

Objectives: Purpose of this study was to evaluate properties of apelin, a peptide detectable in peripheral blood, for atrial fibrillation (AF) detection in a diverse population of patients covering a broad spectrum from healthy to polymorbid patients., Background: AF is the most common cardiac arrhythmia with constantly increasing incidence and prevalence. Currently available diagnostic tools do not provide sufficient detection rate. Large proportion of patients with AF remains undiagnosed and the possibility of screening at-risk groups would be significantly beneficial., Methods: We designed this study as a multi-centre retrospective study. Study population included 183 patients. 64 in non-AF and 119 in AF group., Results: Apelin plasma concentration was significantly lower in AF group compared to non-AF group (p < 0.001). Receiver operating characteristic analysis of apelin as a predictor of AF scored area under the curve of 0.79, sensitivity = 0.941 and specificity = 0.578. Multivariate analysis using logistic regression adjusted for age, BMI, apelin, dilated LV, dilated LA, arterial hypertension, and gender showed only apelin and age to be statistically significant contributors for AF., Conclusion: Apelin might be a promising biomarker for detecting AF in our study population. These results suggest promising potential of apelin as a screening biomarker for AF (Tab. 2, Fig. 1, Ref. 46). Text in PDF www.elis.sk Keywords: biomarker, apelin, arrhythmia, atrial fibrillation.

Western-type diet with high salt and sugar, sedentary behavior, obesity, tobacco and alcoholism are important risk factors for hypertension. This review aims to highlight the role of western diet-induced oxidative stress and inflammation in the pathogenesis of hypertension and the role of various types of diets in its prevention with reference to dietary approaches to stop hypertension (DASH) diet. It seems that it is crucial to alter the western type of diet because such diets can also predispose all CVDs. Western diet-induced oxidative stress is characterized by excessive production of reactive oxygen species (ROS) with an altered oxidation-reduction (redox) state, leading to a marked increase in inflammation and vascular dysfunction. Apart from genetic and environmental factors, one important cause for differences in the prevalence of hypertension in various countries may be diet quality, deficiency in functional foods, and salt consumption. The role of the DASH diet has been established. However, there are gaps in knowledge about the role of some Indo-Mediterranean foods and Japanese foods, which have been found to decrease blood pressure (BP) by improving vascular function. The notable Indo-Mediterranean foods are pulses, porridge, spices, and millets; fruits such as guava and blackberry and vegetables, which may also decrease BPs. The Japanese diet consists of soya tofu, whole rice, in particular medical rice, vegetables and plenty of fish rich in fish oil, fish peptides and taurine that are known to decrease BPs. Epidemiological studies and randomized, controlled trials have demonstrated the role of these diets in the prevention of hypertension and metabolic diseases. Such evidence is still meager from Japan, although the prevalence of hypertension is lower (15-21%) compared to other developed countries, which may be due to the high quality of the Japanese diet. Interestingly, some foods, such as berries, guava, pumpkin seeds, carrots, soya beans, and spices, have been found to cause a decrease in BPs. Omega-3 fatty acids, fish peptide, taurine, dietary vitamin D, vitamin C, potassium, magnesium, flavonoids, nitrate and l-arginine are potential nutrients that can also decrease BPs. Larger cohort studies and controlled trials are necessary to confirm our views.

The goal of this case report is to describe the young childhood cancer survivor who was treated for nonHodgkin lymphoma with chemotherapy containing anthracycline doxorubicin and who developed symptoms of serious cardiovascular damage 27 years after diagnosis of cancer. The patient is in longterm complete remission of the lymphoma. He started guideline medical therapies for chronic heart failure and had a cardioverter defibrillator implanted for primary prevention of sudden cardiac death. He is currently a candidate for heart transplantation.

European Association of Spa Rehabilitation recommend spa rehabilitation for patients with post COVID-19 syndrome (post C-19). We studied effects of special mountain spa rehabilitation program and its combination with ubiquinol (reduced form of coenzyme Q 10 -CoQ 10 ) supplementation on pulmonary function, clinical symptoms, endogenous CoQ 10 levels, and platelet mitochondrial bioenergetics of patients with post C-19. 36 patients with post C-19 enrolled for rehabilitation in mountain spa resort and 15 healthy volunteers representing the control group were included in this study. 14 patients with post C-19 (MR group) were on mountain spa rehabilitation lasting 16-18 days, 22 patients (MRQ group) were supplemented with ubiquinol (2 × 100 mg/day) during the rehabilitation and additional 12-14 days at home. Clinical symptoms and functional capacity of the lungs were determined in the patients before and after the spa rehabilitation program. Platelet bioenergetics by high-resolution respirometry, plasma TBARS concentration, and CoQ 10 concentration in blood, plasma and platelets were evaluated before and after the spa rehabilitation program, and in 8 patients of MRQ group also after additional 12-14 days of CoQ 10 supplementation. Pulmonary function and clinical symptoms improved after the rehabilitation program in both groups, 51.8% of symptoms disappeared in the MR group and 62.8% in the MRQ group. Platelet mitochondrial Complex I (CI)-linked oxidative phosphorylation (OXPHOS) and electron transfer (ET) capacity were markedly reduced in both groups of patients. After the rehabilitation program the improvement of these parameters was significant in the MRQ group and moderate in the MR group. CI-linked OXPHOS and ET capacity increased further after additional 12-14 days of CoQ 10 supplementation. CoQ 10 concentration in platelets, blood and plasma markedly raised after the spa rehabilitation with ubiquinol supplementation, not in non-supplemented group. In the MRQ group all parameters of platelet mitochondrial respiration correlated with CoQ 10 concentration in platelets, and the increase in CI-linked OXPHOS and ET capacity correlated with the increase of CoQ 10 concentration in platelets. Our data show a significant role of supplemented ubiquinol in accelerating the recovery of mitochondrial health in patients with post C-19. Mountain spa rehabilitation with coenzyme Q 10 supplementation could be recommended to patients with post C-19. This study was registered as a clinical trial: ClinicalTrials.gov ID: NCT05178225., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sumbalová, Kucharská, Rausová, Palacka, Kovalčíková, Takácsová, Mojto, Navas, Lopéz-Lluch and Gvozdjáková.)

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant, tendency of increased levels of 8-hydroxy-2’-deoxyguanosine and malondialdehyde in the HRW group. This mild increase may be indicative of the hormetic effects of molecular hydrogen that occurred prior to the significant clinical improvements reported in previous longer-term studies. The favorable trends in this study in conjunction with previous animal and clinical findings suggest that HRW may serve as an important adjuvant therapy for promoting and maintaining optimal health and wellness. Longer term studies focused on prevention, maintenance, or treatment of NAFLD and early stages of NASH are warranted.

Objectives: Non-communicable diseases are estimated to account for 90 % of total deaths and 19 % of premature deaths in Slovakia. Major preventable risk factors of premature mortality are overweight, obesity and alcohol consumption., Background: Screening of risk factors related to alcoholic and nonalcoholic fatty liver diseases (AFLD and NAFLD, respectively) in Slovak outpatients with liver disease., Methods: A total group of 923 patients, aged 19-91 years were included in the study. Self-administered anonymous questionnaires (Q) were filled in by them. Twelve questions were included relating to age, gender, education, BMI, intake of vegetable, fruit, fish, alcohol, and coffee, as well as to smoking and physical exercise., Results: Overweight/obesity was detected in 59 % of patients, insufficient fiber intake in 87 % of patients, insufficient fish intake in 85 % of patients, and insufficient physical exercise in 68 % of patients. BMI over 25 together with the risk of alcohol consumption was present in 68 % of patients. Smoking was present in 19 % of patients and insufficient coffee intake (from its hepatoprotective point of view) was in 35 % of patients. A total proportion of 75 % of patients were at risk for NAFLD. The risk of alcohol consumption was present in 64 % of patients., Conclusions: An anonymous questionnaire is a useful screening tool for searching for the risks of NAFLD and AFLD in general practice. Recommendation of a screening schedule for general practitioners is implemented (Tab. 2, Fig. 4, Ref. 36).

Background: Atrial fibrillation (AF) is associated with high risk of stroke preventable by timely initiation of anticoagulation. Currently available screening tools based on ECG are not optimal due to inconvenience and high costs. Aim of this study was to study the diagnostic value of apelin for AF in patients with high risk of stroke. Methods: We designed a multicenter, matched-cohort study. The population consisted of three study groups: a healthy control group (34 patients) and two matched groups of 60 patients with high risk of stroke (AF and non-AF group). Apelin levels were examined from peripheral blood. Results: Apelin was significantly lower in AF group compared to non-AF group ( 0.694 ± 0.148 vs. 0.975 ± 0.458 ng/ml, p = 0.001) and control group ( 0.982 ± 0.060 ng/ml, p < 0.001), respectively. Receiver operating characteristic (ROC) analysis of apelin as a predictor of AF scored area under the curve (AUC) of 0.658 . Apelin's concentration of 0.969 [ng/ml] had sensitivity = 0.966 and specificity = 0.467 . Logistic regression based on manual feature selection showed that only apelin and NT-proBNP were independent predictors of AF. Logistic regression based on selection from bivariate analysis showed that only apelin was an independent predictor of AF. A logistic regression model using repeated stratified K-Fold cross-validation strategy scored an AUC of 0.725 ± 0.131. Conclusions: Our results suggest that apelin might be used to rule out AF in patients with high risk of stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bohm, Snopek, Tothova, Bezak, Jajcay, Vachalcova, Uher, Kurecko, Kissova, Danova, Olejnik, Michalek, Hlavata, Petrikova, Mojto, Kyselovic and Farsky.)

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimunne disorder affecting both small and large synovial joints, leading to their destruction. Platelet biomarkers are involved in inflammation in RA patients. Increased circulating platelet counts in RA patients may contribute to platelet hyperactivity and thrombosis. In this pilot study we evaluated platelet mitochondrial bioenergy function, CoQ10 levels and oxidative stress in RA patients., Methods: Twenty-one RA patients and 19 healthy volunteers participated in the study. High resolution respirometry (HRR) was used for analysis of platelet mitochondrial bioenergetics. CoQ10 was determined by HPLC method; TBARS were detected spectrophotometrically., Results: Slight dysfunction in platelet mitochondrial respiration and reduced platelet CoQ10 levels were observed in RA patients compared with normal controls., Conclusions: The observed decrease in platelet CoQ10 levels may lead to platelet mitochondrial dysfunction in RA diseases. Determination of platelet mitochondrial function and platelet CoQ10 levels could be used as new diagnostic strategies for mitochondrial bioenergetics in rheumatoid diseases., Competing Interests: The authors have declared that no competing interests exist.

Objective: This single-arm real-world observation aims to examine the effects of empagliflozin (EMPA) on coronary risk factors among subjects with known diabetes., Materials and Methods: Records of 63 subjects with type 2 diabetes mellitus, receiving EMPA were drawn for this study. Of 63 patients with diabetes, 6 were excluded, and the remaining 57 received EMPA (25 mg/day) for 24 weeks. Clinical data, dietary intakes, and physical activity were assessed by validated questionnaires., Results: Treatment with EMPA was associated with significant decline in fasting and 2-hour post-prandial blood glucose and Hb1c indicating that this agent has potential antidiabetic effects. Pro-inflammatory cytokines; C-reactive protein, TNF-α, and interleukin-6 showed significant reduction after treatment with EMPA, compared to baseline levels. Apart from these changes, parameters of oxidative stress, thiobarbituric acid reactive substances, malondialdehyde, and diene conjugates as well as uric acid, showed a significant decline with an increase in antioxidant vitamins A, E, and C and beta-carotene as well as nitrite. There was a significant decline in serum uric acid, systolic and diastolic blood pressures, and angiotensin-converting enzyme (ACE), with a non-significant reduction in body weight and body mass index as well as in waist circumference of modest significance, after intervention of 12 weeks compared to baseline levels. Total cholesterol, VLDL cholesterol and triglycerides showed non-significant decline compared to baseline levels., Conclusion: It is possible that EMPA administration can cause a significant decline in pro-inflammatory cytokines along with blood glucose, Hb1c, oxidative stress, uric acid, blood pressures, and ACE with an increase in antioxidant vitamins and nitrite. Randomized, controlled intervention trials would be necessary to confirm our findings.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and a decrease of glomerular filtration rate. Reduced mitochondrial function, coenzyme Q 10 (CoQ 10 ), and increased oxidative stress in patients with CKD contribute to the disease progression. We tested whether CoQ 10 levels, oxidative stress and platelet mitochondrial bioenergetic function differ between groups of CKD patients., Methods: Twenty-seven CKD patients were enrolled in this trial, 17 patients had arterial hypertension (AH) and 10 patients had arterial hypertension and diabetes mellitus (AH and DM). The control group consisted of 12 volunteers. A high-resolution respirometry (HRR) method was used for the analysis of mitochondrial bioenergetics in platelets, and an HPLC method with UV detection was used for CoQ 10 determination in platelets, blood, and plasma. Oxidative stress was determined as thiobarbituric acid reactive substances (TBARS)., Results: Platelets mitochondrial respiration showed slight, not significant differences between the groups of CKD patients and control subjects. The oxygen consumption by intact platelets positively correlated with the concentration of CoQ 10 in the platelets of CKD patients., Conclusion: A decreased concentration of CoQ 10 and oxidative stress could contribute to the progression of renal dysfunction in CKD patients. The parameters of platelet respiration assessed by high-resolution respirometry can be used only as a weak biological marker for mitochondrial diagnosis and therapy monitoring in CKD patients.

Experimental studies indicate that energy homeostasis to the circadian clock at the behavioral, physiological, and molecular levels, emphasize that timing of food intake may play a significant role in the development of obesity and central obesity. Therefore, resetting the circadian clock by circadian energy restriction via food intake in the morning or evening, may be used as a new approach for prevention of obesity, metabolic syndrome and related diseases. After ethical clearance and written, informed consent, free living subjects were included if they volunteered to take most of the total daily meals (approximately 2000 Kcal./day) in the evening (4 weeks) or morning (4 weeks). Of 22 adults, half were randomly selected by computer generated numbers to eat in the morning and the other half in the evening, after 8.00 PM. The eating pattern was changed after 4 weeks of intervention and a 4-week washout period, those who ate in the morning were advised to eat in the evening and vice versa. Validated questionnaires were used to assess food intakes, physical activity, and intake of alcohol and tobacco. Physical examination included measurement of body weight, height, and blood pressure (BP) by sphygmomanometer. Data were regularly recorded blindly, in all subjects at start of study and during follow-up. Blood samples were collected after an overnight fast for analysis of blood glucose and Hb1c. Feeding in the evening was associated with significant increase in body weight by 0.80 kg ( P < .001), body mass index (BMI) by 0.30 kg/m 2 ( P < .001) and waist circumference by 1.13 cm ( P < .05). Feeding the same amount of energy in the morning was not associated with any significant change in weight, BMI or waist circumference ( P > .500). Lesser increases in all three variables were associated with AM versus PM feeding ( P < .05). Systolic BP slightly increased on PM and decreased on AM feeding, with a difference between the two responses of 1.55 mmHg ( P < .05). Fasting blood glucose was lower on AM than on PM feeding (74.86 vs. 77.95 mg/dl, paired t = 4.220, P < .001). Hb1C increased on PM feeding by 0.28 (from 4.45 to 4.73; t = 9.176, P < .001), but decreased on AM feeding by 0.077 (from 4.53 to 4.45; t = -6.859, P < .001). The difference in Hb1C response between AM and PM feeding is also statistically significant (t = -11.599, P < .001). Eating in the evening can predispose to obesity, central obesity and increases in fasting blood glucose and Hb1c that are indicators of the metabolic syndrome. By contrast, eating in the morning can decrease Hb1c and systolic BP, indicating that it may be protective against the metabolic syndrome.

Objectives: The mortality of patients with chronic kidney diseases (CKD) increases with the decrease in glomerular filtration rate (eGFR). In the progress of CKD that is closely linked to non-communicable diseases (NCDs), the role of coenzyme Q10 (CoQ10) is not fully evaluated. We aimed to evaluate the importance of CoQ10, CoQ10/cholesterol ratio, and oxidative stress in the progress of CKD., Patients and Methods: The control group was constituted of 19 healthy subjects who volunteered to enrol in the study, CKD group consisted of 58 patients with CKD, of whom 54 had CKD combined with hypertension, 22 had CKD combined with hypertension and diabetes type 2 , and 18 had CKD combined with hypertension and statin therapy. We observed age, BMI, creatinine, uric acid, eGFR, hemoglobin, CRP, glucose, lipids fraction, and liver enzymes. Coenzyme Q10-TOTAL (ubiquinol+ubiquinone) in platelets and plasma were determined using HPLC method with UV detection. Indexed of CoQ10/lipid fractions were evaluated. Oxidative stress was determined as thiobarbituric acid‑reactive substances (TBARS)., Results: With increased stages of CKD, eGFR and CoQ10 as well as its ratio to lipids were significantly reduced while TBARS increased., Conclusion: We assume that lower endogenous CoQ10 level may be one of the reasons of kidney dysfunction. CoQ10/lipids ratio and increase in oxidative stress can predict the progression of CKD in patients with arterial hypertension, diabetes mellitus and dyslipidemia (Tab. 2, Fig. 4, Ref. 49).

Seasonal variations in temperature may influence the physiological and pathological metabolic pathways, concentrations of antioxidants, degree of oxidative stress and mitochondrial function. The aim of this study was to evaluate platelet mitochondrial function in human subjects during seasonal variations in temperature. Two groups of healthy young subjects were enroled in the study. Winter group, mean outside temperature was 4.77°C and Spring group, mean outside temperature was 24.32°C. High-resolution respirometry method was used for determination of mitochondrial respiration and oxidative phosphorylation in platelets. Concentrations of coenzyme Q10 (CoQ10) and tocopherols were determined in platelets, blood and plasma. Our data showed slightly (not significantly) reduced respiration in intact platelets, basal and ADP-stimulated mitochondrial respiration at Complex I, as well as CoQ10-TOTAL and α-tocopherol concentrations in winter. The concentration of γ-tocopherol was higher in winter. Platelet mitochondrial ATP production depended on platelet CoQ10-TOTAL concentration in winter, not in spring. We conclude that seasonal temperature participates in the mechanism of platelet mitochondrial respiratory chain function and oxidative phosphorylation that depends on their CoQ10-TOTAL concentration at lower winter outside temperature. CoQ10 supplementation may improve platelets mitochondrial ATP production at winter season. High-resolution respirometry offers sensitive method for detection of changes of platelets mitochondrial respiratory function.

Alpha-1-acid glycoprotein (AGP) is a glycoprotein found in the alpha-1 globulin fraction of human plasma proteins. AGP is an important representative of acute-phase proteins. Although numerous articles have been devoted to AGP, its exact biological function remains obscure. AGP levels increase with a number of diseases. One of them is a tumor disease. In our paper, we discuss the role of increased AGP levels in cancer patients. We deal with the role of AGP as a drug-binding protein and its effect on the efficacy of chemotherapy in oncological patients. Other problems that are discussed in our paper include the role of AGP as an immunomodulatory protein and its relationship to angiogenesis because angiogenesis plays an important role in the progression of cancer (Ref. 57). Keywords: alpha-1-acid glycoprotein, orosomucoid, cancer, disease marker, immunomodulatory protein,drug-binding protein.

Objectives: To test the hypothesis if mitochondrial bioenergetic function analyzed in circulating platelets may represent peripheral signature of mitochondrial dysfunction in nephropathy associated to non-communicable human diseases such as cardiovascular diseases, diabetes and with statins treatment., Methods: High-resolution respirometry was used for analysis of mitochondrial bioenergetics in human platelets isolated from peripheral blood. This method is less-invasively compared to skeletal muscle biopsy. Patients with nephropathies and in combination with non-communicable diseases were included in the study., Results: This pilot study showed platelet mitochondrial bioenergy dysfunction in patients with nephropathies and non-communicable diseases. Positive effect of treatment with 10 mg atorvastatin on platelet mitochondrial respiratory chain Complex I-linked respiration and ATP production in patients with nephropathies, diabetes and 80 mg atorvastatin in patient with nephropathy and dialysis was found. Positive effect of 80 mg fluvastatin treatment, and negative effect of thrombocytopenia and renal transplantation on platelet mitochondrial bioenergy was determined., Conclusion: High-resolution respirometry allowed detection of small changes in platelet mitochondrial function. This method could be used as a sensitive bioenergetic test of mitochondrial function for diagnosis and monitoring the therapy in patients with nephropathy (Tab. 1, Fig. 3, Ref. 39).

The study aims to examine the effects of coenzyme Q10, (a bioenergetic antioxidant), on the indexes of left ventricular remodeling, oxidative damage, and angiotensin-converting enzyme (ACE) level after acute myocardial infarction (AMI) with left ventricular dysfunction. In a double blind, randomized, placebo-controlled, parallel group study (a retrospective analysis of an earlier trial) in 55 patients with left ventricular ejection fraction <50% after AMI, the effects of coenzyme Q10 (120 mg/day) or placebo were studied for 24 weeks. Two-dimensional echocardiography was performed at discharge, (approximately 5⁻10 days after admission) and at 6 months after AMI. The results revealed that wall thickness opposite the site of infarction decreased from (mean ± standard deviation (SD)) 12.2 ± 2.0 mm to 10.0 ± 1.8 mm with coenzyme Q10 compared with 12.8 ± 2.2 mm to 13.3 ± 2.3 mm with placebo ( p < 0.01). Left ventricular mass changed from 236 ± 72 g to 213 ± 61 g with coenzyme Q10 compared with 230 ± 77 g to 255 ± 86 g with placebo ( p < 0.01). Treatment with coenzyme Q10 also prevented alteration of sphericity index which is a ratio of the long and short axis of the left ventricle (which changed from 1.61 ± 0.28 to 1.63 ± 0.30 with coenzyme Q10 compared with 1.61 ± 0.32 to 1.41 ± 0.31 with placebo ( p < 0.05)). Coenzyme Q10 also prevented alteration of the wall thickening abnormality at the infarct site, which changed from 9.4 ± 3.0 cm² to 9.1 ± 2.8 cm² compared with 10.1 ± 3.1 to 13.7 ± 4.2 cm² with placebo ( p < 0.05). End diastolic and systolic volumes also showed significant reduction with coenzyme Q10 compared to placebo. The serum level of ACE showed significant decline in the coenzyme Q10 group compared to the control group. Treatment with coenzyme Q10 early after AMI causes attenuation of left ventricular remodeling and decreases the serum ACE level in patients with left ventricular dysfunction.

Objective: The aim of the study was to observe the influence of 11-days complete water fasting (WF) and regeneration diet (RD) on renal function, body weight, blood pressure and oxidative stress., Background: Therapeutic WF is considered a healing method., Methods: Ten volunteers drank only water for 11 days, followed by RD for the next 11 days. Data on body weight, blood pressure, kidney functions, antioxidants, lipid peroxidation, cholesterols, triacylglycerols and selected biochemical parameters were obtained., Results: WF increased uric acid and creatinine and decreased glomerular filtration rate. After RD, the parameters were comparable to baseline values. Urea was not affected. Lipid peroxidation (TBARS) decreased and maintained stable after RD. Fasting decreased α-tocopherol and increased γ-tocopherol, no significant changes were found after RD. Coenzyme Q10 decreased after RD. HDL-cholesterol decreased in WF. Total- and LDL-cholesterol decreased after RD. Other biochemical parameters were within the range of reference values., Conclusions: The effect of the complete fasting on kidney function was manifested by hyperuricemia. Renal function was slightly decreased, however maintained within the reference values. After RD, it returned to baseline values. The positive effect of the complete water fasting was in the reduction of oxidative stress, body weight and blood pressure (Tab. 3, Ref. 25).

Background: Liver fibrosis is the final common pathway of chronic liver diseases of various etiology. From the practical standpoint, it would be ideal to have a noninvasive fibromarker. The aim of our study was to investigate the levels of alpha-2-macroglobulin, potential fibromarker, in correlation to histological staging and another potential fibromarker, hyaluronic acid, in patients with chronic hepatitis C., Methods: Population groups in this study consisted of 51 healthy volunteers and 54 patients with chronic hepatitis C. Liver biopsies were obtained under ultrasound guidance. Alpha-2-macroglobulin was determined by electroimmunodiffusion and hyaluronic acid with enzyme-linked binding protein assay., Results: Both potential fibromarkers, alpha-2-macroglobulin and hyaluronic acid, were increased in patients with chronic hepatitis C. The alpha-2-macroglobulin levels were not significantly increased in the groups F0-F1. In the groups F2-F4, alpha-2-macroglobulin levels were significantly higher than in the control group. The changes of hyaluronic acid were similar to changes of alpha-2-macroglobulin. Regression analysis showed a significant correlation between hyaluronic acid and alpha-2-macroglobulin levels., Conclusions: According to the results of our study, it can be concluded that alpha-2-macroglobulin and hyaluronic acid might be useful markers of liver fibrosis (Tab. 2, Ref. 15).

Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with captopril and melatonin. 12-week-old male Wistar rats were divided into the following groups: controls, ivabradine (10 mg/kg/24 h), L-NAME (40 mg/kg/24 h), L-NAME + ivabradine, L-NAME + captopril (100 mg/kg/24 h), L-NAME + melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff method once a week. The behaviour of rats was investigated during 23-hours in the phenotyper after four weeks of the treatment. Chronic administration of L-NAME induced hypertension without a change in HR. All tested substances partly prevented the increase of SBP, while ivabradine and melatonin also reduced HR. Ivabradine, captopril and melatonin reduced daily food intake, slightly decreased daily water intake and attenuated body weight gain. In L-NAME group, locomotor activity was enhanced by ivabradine, whereas exploratory behaviour was increased by melatonin and captopril. In conclusion, ivabradine, besides its potentially protective hemodynamic actions, does not seem to exert any disturbing effects on behaviour in L-NAME-induced hypertension in rats, while some of its effects were similar to captopril or melatonin. It is suggested that ivabradine used in cardiovascular indications is harmless regarding the effect on behaviour.

Objective: To evaluate the threshold limit of vitamin D3 associated with the risk of nonskeletal health complications in humans., Background: Vitamin D3 deficiency is primary caused by a reduced sun exposure, consequent limiting of vitamin D3 production in the skin, and low intake of food with this vitamin., Methods: Ninety-two adults (25-95 years old) were admitted to III. Internal clinic or examined in outpatient department of The University hospital in Bratislava. Vitamin D3 levels were determined using electrochemical luminescence immunoassay. The least square method for the results processing was used., Results: Vitamin D3 level 16 ng/ml may be threshold limit for the risk of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. A higher occurrence of the observed diseases was in female and male patients with vitamin D3 levels<16 ng/ml.The highest increase of occurrence of diabetes mellitus in women for vitamin D3<16 ng/ml (160%) compared to vitamin D3≥16 ng/ml (40%) was observed. Concerning the men, the highest increase refers to ischaemic heart disease (67%)., Conclusion: The limit value of vitamin D3, 16 ng/ml, confirmed the association between vitamin D3 insufficiency and the presence of hypertension, ischaemic heart disease, renal insufficiency and diabetes mellitus. Its relation to age, sex and other variables was detected (Tab. 1, Fig. 5, Ref. 27).

Objectives: This study indicates that the seasonality of births of patients with DM1 and DM2 has occurred in their adolescence or adulthood., Background: Patients with Diabetes mellitus type 2 (DM2) with the maturity onset have different seasonal birth patterns from those with Diabetes mellitus type 1 (DM1) with the maturity onset, or DM1children., Methods: Monthly numbers of births of 81 and 236 children with DM1 and DM2, respectively, in adolescent or adult age, were adapted to different actual length of calendar months. The 12- and 6-month rhythm was tested using the cosinor regression with 95% confidence interval versus the hypothesis of null seasonality., Results: Regarding DM1 with maturity onset, annual and semiannual rhythm was significant in both genders, with the increase in birth numbers from November to January and decrease in March, April and August. In DM2, only female data displayed a significant annual rhythm, with an increase in birth from April to August and decrease from October to December.  CONCLUSION: The birth seasonality related to DM1 in adolescent or adult age appears to be reciprocal, compared to DM1 in childhood. For DM2, the seasonality of births was found only in females. The increase in female fecundity seems to be related to an increase in the risk of DM2 in female offspring. The outcomes could help in identifying environmental and endogenous factors related to seasonality cycle (Tab. 1, Fig. 1, Ref. 18).

This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30 min after 1 mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p ≪ 0.001 and p = 0.002, respectively) was observed. The high correlation (r = 0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ(10-TOTAL), γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ(10-TOTAL) (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ(10-TOTAL), and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

Introduction: Diabetes mellitus is associated with a lot of changes in intermediary metabolism and several authors reported on higher frequency of liver diseases in patients with diabetes., Aim of the Study: Was to establish the changes of blood serum cholinesterase, prealbumin and albumin, parameters which are accepted as an index of liver proteosynthetic function, in patients with diabetes mellitus., Patients and Methods: The study group consisted of 207 patients with diabetes mellitus (83 patients with type I and 124 patients with type II diabetes mellitus). Control group consisted of 179 healthy subjects. The activity of cholinesterase was assayed by the kinetic method, concentrations of prealbumin and albumin were determined immunochemically., Results: Activity of serum cholinesterase was significantly higher in group of patients with diabetes mellitus than in control group (65.05 vs 73.33 microkat/l). The concentration of prealbumin was lower in blood serum of patients with diabetes than in controls (308.10 vs 285.85 mg/l). Serum levels of albumin were not different in both studied groups. After dividing of patients according to the type of diabetes, 80 % of abnormal values of cholinesterase and prealbumin were present in patients with type II diabetes., Conclusions: The results of our study showed abnormal values of determined liver tests approximately in 22 % of patients with diabetes mellitus. The character of laboratory changes--increased activity of cholinesterase, decreased concentration of prealbumin and normal levels of albumin, suggests development of liver steatosis in these patients. The most of pathological findings were in patients with diabetes type II (Tab. 3, Ref. 20).