Serum trace element levels and activity of enzymes associated with oxidative stress in endometriosis and endometrial cancer.

Endometriosis and endometrial cancer are closely related to oxidative stress. However, the direct relationship between copper and zinc levels and oxidative stress in the extracellular and intracellular space remains unclear. The presented study is focused on the determination of serum Zn and Cu levels, glutathione concentration and enzyme activity in three groups: patients diagnosed with endometrial cancer (EC), patients diagnosed with endometriosis (EM), and a healthy control group. Spectrophotometric determination of trace elements revealed that levels of zinc and copper were lower in blood plasma of patients with endometriosis as compared with the other groups; however, there were no significant differences in the Cu/Zn ratio. Furthermore, significantly increased blood serum glutathione levels were detected in both EM and EC groups compared with the control group. While the activity of superoxide dismutase (SOD) was similar across the studied groups, we observed differences in the activity of other enzymes associated with oxidative stress, including glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), between the control group and the EM and EC patients. Additionally, analysis of gene expression based on free circulating mRNA indicated significant differences in the expression of SOD isoenzymes between the patient groups and the control group; expression of GPx isoenzymes was also altered. Obtained results may have potential application in diagnostics as well as monitoring of endometriosis and endometrial cancer.

Serum Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

BACKGROUND: This work aims to study the effect of reductions in various body mass components on the oxidative, glycemic, and lipid parameters of people with obesity (PWO). METHODS: A total of 53 PWO underwent a six-month individualized low-calorie diet combined with moderate exercise, during which anthropometric, biochemical, and oxidative parameters were measured. Probands were divided into groups based on weight, visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses. RESULTS: Weight reduction normalizes glycemia, but VFA reduction is less pronounced, while SMM and TBW reductions are more pronounced in patients with higher initial concentrations of glucose and fructosamine. Moreover, changes in oxidative parameters correlate with changes in glucose. CONCLUSIONS: Weight loss, regardless of the reduced tissue, decreases cardiovascular risk. We observed a significant change in almost all parameters related to the redox state. In general, parameters responsible for antioxidant action improved, and markers of oxidative damage decreased. Malondialdehyde, lipid peroxides, and total oxidative status levels can be considered biomarkers reflecting only the current severity of reactive oxygen species genesis processes. When considering the glycemic state, the results are not as clear due to the substantial differences between normoglycemic and hyperglycemic patients. Glycemic status is a factor playing a crucial role in weight reduction.

Visualization of the composition of the urinary fluorescent metabolome. Why is it important to consider initial urine concentration?

Urine is a highly complex fluorescent system, the fluorescence of which can be affected by many factors, including the often-ignored initial urine concentration in comprehensive fluorescent urine analysis. In this study, a total urine fluorescent metabolome profile (uTFMP) was created as a three-dimensional fluorescence profile of serial synchronous spectra of urine diluted by geometric progression. uTFMP was generated using software designed for this purpose after recalculating the 3D data concerning the initial urine concentration. It can be presented as a contour map (top view) or as a more illustrative and straightforward simple curve, thus usable in various medicinal applications.

Flavonoids as Promising Natural Compounds in the Prevention and Treatment of Selected Skin Diseases.

Phytochemicals represent a large and diverse group of naturally occurring compounds, bioactive nutrients, or phytonutrients produced by plants, widely found in fruits, vegetables, whole grains products, legumes, beans, herbs, seeds, nuts, tea, and dark chocolate. They are classified according to their chemical structures and functional properties. Flavonoids belong to the phenolic class of phytochemicals with potential solid pharmacological effects as modulators of multiple signal transduction pathways. Their beneficial effect on the human body is associated with their antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic properties. Flavonoids are also widely used in various nutritional, pharmaceutical, medical, and cosmetic applications. In our review, we discuss the positive effect of flavonoids on chronic skin diseases such as vitiligo, psoriasis, acne, and atopic dermatitis.

Salivary Redox Homeostasis in Human Health and Disease.

Homeostasis is a self-regulatory dynamic process that maintains a stable internal environment in the human body. These regulations are essential for the optimal functioning of enzymes necessary for human health. Homeostasis elucidates disrupted mechanisms leading to the development of various pathological conditions caused by oxidative stress. In our work, we discuss redox homeostasis and salivary antioxidant activity during healthy periods and in periods of disease: dental carries, oral cavity cancer, periodontal diseases, cardiovascular diseases, diabetes mellitus, systemic sclerosis, and pancreatitis. The composition of saliva reflects dynamic changes in the organism, which makes it an excellent tool for determining clinically valuable biomarkers. The oral cavity and saliva may form the first line of defense against oxidative stress. Analysis of salivary antioxidants may be helpful as a diagnostic, prognostic, and therapeutic marker of not only oral, but also systemic health.

Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma.

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer to evade immune surveillance. Altered tryptophan metabolism was studied in patients with pigmented malignant melanoma confirmed histologically by the anatomic stage grouping for cutaneous melanoma using clinical staging on the basis of the Breslow thickness of the melanoma, the degree of spread to regional lymph nodes, and by the presence of distant metastasis. (2) Methods: Urinary tryptophan metabolites were detected by RP-HPLC method. (3) Results: In the present work, we provided evidence of altered metabolism of all tryptophan pathways in melanoma patients. (4) Conclusions: Knowledge of the shifted serotonin pathway toward DHICA formation and kynurenine pathway shifted toward NAD+ production could serve in the early detection of the disease and the initiation of early treatment of malignant melanoma.

Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients.

Weight loss is recommended for obese patients with cardiovascular risk; however, it remains questionable how hyperglycemia affects this process. To address this problem, we aimed to determine the association between weight loss, lipid profile, and body mass parameters in obese normoglycemic and hyperglycemic patients. Obese (body mass index30 kg/m2) normoglycemic and hyperglycemic volunteers were placed on a weight reduction program that included a balanced, low-calorie diet and moderate exercise for 6 months. Participants were assessed for serum glucose, ß-cell functions, insulin resistance, lipid metabolism, lipoprotein profile, and body mass parameters. This weight reduction program fully normalized serum glucose levels only in a subpopulation of patients. These individuals also exhibited a significant reduction in body weight, and significant improvement in serum lipid profile and insulin resistance. In contrast, the patients that remained hyperglycemic were characterized by persistent insulin resistance, increased levels of atherogenic fractions of LDL and HDL lipoproteins, and elevated values of a modified Atherogenic Index of Plasma. Correlation analysis indicated a strong positive association between the modified Atherogenic Index of Plasma with atherogenic lipid profile, insulin resistance, and body mass parameters, indicating its usefulness in clinical studies in obese patients. Overall, our data indicate that successful treatment of hyperglycemia facilitates weight loss and improves the composition of blood lipids, while persisting hyperglycemia negatively affects the weight loss process and maintains an atherogenic lipid profile. Because hyperglycemia predisposes to cardiovascular disorders, its correction should be the primary goal during weight reduction therapy.

Loss of Skeletal Muscle Mass and Intracellular Water as Undesired Outcomes of Weight Reduction in Obese Hyperglycemic Women: A Short-Term Longitudinal Study.

The current study is focused on the influence of hyperglycemia on weight loss in obese premenopausal women. Specifically, the study evaluated the impact of a six-month individualized low-calorie diet combined with moderate exercise on weight reduction and glucose metabolism in obese women with normoglycemia compared to obese women with moderate hyperglycemia. The results indicated that patients with normoglycemia achieved a successful weight loss, which was connected to a decrease in adipose tissue and reflected by diminished content of visceral fat area (VFA) and percent body fat. In contrast, weight reduction in patients with hyperglycemia was connected not only to the loss of VFA but also to undesired decrease in skeletal muscle mass as well as intracellular and total body water. These unfavorable outcomes were observed despite normalization of glucose metabolism reflected by statistically significant lowering glucose, fructosamine, advanced glycation end-products, and HOMA-IR levels. Overall, the obtained results indicate the importance of the measurement of the carbohydrate profile in obese women and the need for an early introduction of weight reduction strategies before the development of hyperglycemia.

The Effect of Oestrogen Supplementation on Antioxidant Enzymes and Mitochondrial Respiratory Function After Myocardial Infarction of Ovariectomized Rats.

ABSTRACT: Acute myocardial infarction (MI) is the leading cause of mortality worldwide with premenopausal women showing a lower incidence of cardiovascular disease compared with men of the same age. After menopause, this advantage disappears, suggesting that sex hormones play a cardioprotective role. This study was aimed to assess on the activity of antioxidant enzymes in plasma and the respiratory function of isolated heart mitochondria after the induction of MI in rats after ovariectomy and estradiol benzoate supplementation. Sprague-Dawley female rats were ovariectomized 3 months before the induction of MI and supplemented/not supplemented with oestrogen 3 months before/7 days after the induction of MI. No significant differences in glutathione peroxidase activities were found in any group. Differences between values were only significant in the ovariectomized not supplemented group (P < 0.01) for the glutathione reductase activity and glutathione concentrations. In isolated mitochondria (7 days after MI), the decline in respiration was observed comparing the ovariectomized and nonovariectomized group. Respiratory functions did not show significant differences between animals supplemented with oestrogen before MI or treated with oestrogen after MI. Ovariectomy worsened mitochondrial dysfunction after MI, and oestrogen supplementation before or after the induction of MI did not improve mitochondrial function.

Current View on the Mechanisms of Alcohol-Mediated Toxicity.

Alcohol is a psychoactive substance that is widely used and, unfortunately, often abused. In addition to acute effects such as intoxication, it may cause many chronic pathological conditions. Some of the effects are very well described and explained, but there are still gaps in the explanation of empirically co-founded dysfunction in many alcohol-related conditions. This work focuses on reviewing actual knowledge about the toxic effects of ethanol and its degradation products.

Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma.

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence.

Native fluorescence of tear fluid as a tool for diagnostics of glaucoma.

Glaucoma is one of the leading causes of irreversible vision loss worldwide. There is an enormous need for the detection of its early stages and also speeding up and simplifying regular examinations. Among the new diagnostic approaches, the use of tear fluid has been intensively investigated in recent years. For this purpose, we analyzed the tear fluid of patients with glaucoma and related diseases. To sensitively capture the subtle ocular abnormalities related to glaucoma and manifested in tear fluid, we used synchronous fluorescence spectroscopy. In this observational case-control study, we detected significant differences in the intensity of tear fluid fluorescence located at λ ex/Δλ = 280/70 nm between the groups of primary open-angle glaucoma (p < 0.01), suspected glaucoma (p < 0.0001), and ocular hypertension (p < 0.05), when compared to the healthy control group. The signal was not significantly higher in women than in men (p = 0.05), and no correlation was found with age (r = -0.05, p > 0.05), nor treatment (p > 0.05). Taken together, tear fluid fluorescence could serve as a discriminative parameter between patients with glaucoma, related diseases, and healthy control subjects and might contribute to the improvement of diagnostics of these diseases.

Recommendations for safe collection of venous blood by a closed collection system.

In recent years, data have been repeatedly published stating that most errors in the process of obtaining a laboratory result occur in the pre-analytical phase (46 % to 68.2 %). This is an area that is usually out of direct control of the laboratory, involving venous blood collection (phlebotomy). The detection of these errors is considered to be quite difficult and can therefore easily lead to a misinterpretation of laboratory results with a consequent adverse effect for the patient and even in unintended injury. The most effective way to prevent them is to have a good knowledge of the current blood collection recommendations, which were recently (2018) revised by the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) and are offered in this review.

Specific Urinary Metabolites in Malignant Melanoma.

Background and objectives: Melanin, which has a confirmed role in melanoma cell behaviour, is formed in the process of melanogenesis and is synthesized from tryptophan, L-tyrosine and their metabolites. All these metabolites are easily detectable by chromatography in urine. Materials and Methods: Urine samples of 133 individuals (82 malignant melanoma patients and 51 healthy controls) were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC). The diagnosis of malignant melanoma was confirmed histologically. Results: Chromatograms of melanoma patients showed increased levels of 5,6-dihydroxyindole-2-carboxylic acid, vanilmandelic acid, homovanilic acid, tryptophan, 5-hydroxyindole-3-acetic acid, and indoxyl sulphate compared to healthy controls. Concentration of indoxyl sulphate, homovanilic acid and tryptophan were significantly increased even in the low clinical stage 0 of the disease (indoxyl sulphate, homovanilic acid and tryptophan in patients with clinical stage 0 vs. controls expressed as medium/ interquartile range in µmol/mmol creatinine: 28.37/15.30 vs. 5.00/6.91; 47.97/33.08 vs. 7.33/21.25; and 16.38/15.98 vs. 3.46/6.22, respectively). Conclusions: HPLC detection of metabolites of L-tyrosine and tryptophan in the urine of melanoma patients may play a significant role in diagnostics as well as a therapeutic strategy of melanoma cancer.

Prognostic Value of the Modified Atherogenic Index of Plasma during Body Mass Reduction in Polish Obese/Overweight People.

Although weight loss is recommended for obese patients, it remains questionable how much weight loss is optimal. A novel index that accurately determines the risk of cardiovascular diseases (CVDs) in terms of weight loss is needed. The modified Atherogenic Index of Plasma (AIP), presented here is unique in the literature. It is calculated based on data for anti-atherogenic, high-density lipoprotein cholesterol (HDL-C) fractions, instead of the total HDL-C. This study investigates whether weight loss correlates with CVD risk, and whether the modified AIP allows more accurate diagnostics in obese/overweight people. According to the increase or decrease of AIP during weight loss, 52 Polish patients were subdivided into two groups: group I (increased AIP; n = 16) and group II (decreased AIP; n = 36). The patients' body mass composition and fasting serum lipid parameters (total cholesterol, triglycerides, HDL-C, and LDL-C (low-density lipoprotein cholesterol)), and cholesterol in 21 lipoprotein sub-fractions were determined. Over six months, all patients reduced their body mass by about 10%. There were no significant differences in anthropometric measures between groups. Increases in large and intermediate HDL-C fractions 1 to 6 and decreases in smaller fractions 7 to 10 were observed in group II. In group I, HDL-C fractions 1 and 10 decreased, while cholesterol in other fractions increased. Increases were observed in the antiatherogenic HDL-C of 52% of group II and 4% of group I. As for atherogenic HDL-C, a decrease of 24% was observed in group II and an increase of 9% in group I. In group I, increases of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and large LDL fractions were noticed, and the reverse in group II. The results show that the modified AIP is a more accurate indicator of CVD risk than existing indices, and that uncontrolled weight reduction does not necessarily have a beneficial influence, and may adversely affect the cardiovascular system.

Lipoprotein-Cholesterol Fractions in Marginalized Roma versus Majority Population.

The trend of modern clinical biochemistry is to emphasize the composition and the quality of lipoproteins over their quantity. The serum lipoprotein fractions and subfractions were analyzed by the Lipoprint Lipoprotein Subfractions Testing System, the parameters of lipid profile, as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triacylglycerides (TAG) were determined by an automated selective biochemical analyzer. Our results showed a significantly lower concentration of cholesterol in the LDL fractions 1 and 2 and in the HDL fractions 8 to 10 in Roma compared to the majority population. The most significant differences between Roma and the majority population when considering body mass index (BMI), waist-to-hip ratio and the index of central obesity were in very low-density lipoproteins (VLDL), intermediate-density lipoproteins, fraction A (IDL-A) and LDL-2. The last two listed were significantly higher in the majority population. VLDL was significantly higher in overweight or obese Roma men and in Roma men with central obesity compared to men from the majority population, as well as in Roma women with normal weight and physiological waist-to-hip ratio compared to the women from majority population. Our study is among the first describing the distribution of lipoprotein subfractions in different ethnic groups.

The use of native fluorescence analysis of synovial fluid in the diagnosis of medial compartment disease in medium- and large-breed dogs.

We assumed that proteins are most likely responsible for synovial fluid fluorescence and that changes detected in fluorescence intensity are most likely the result of changes in the concentration of fluorescent proteins. Synchronous fluorescent matrices from synovial fluid samples were measured in the excitation wavelength range of 200-350 nm using a luminescence spectrophotometer. The synchronous matrix of synovial fluid consists of 2 dominant fluorescent centers (F1 and F2) in the ultraviolet region. The fluorescence intensities of both centers were significantly higher in pathological samples, with p = 0.001 (a 59% increase of the median value) for the F1 center and p = 0.002 (a 52% increase of the median value) for the F2 center. Receiver operating characteristic analysis confirmed that synovial fluid autofluorescence is a significant predictor of medial compartment disease in dogs, with the area under the curve at 0.776 (F1) and 0.778 (F2). We did not detect any differences in the autofluorescence of synovial fluid between male and female, or any breed-based changes. No position changes of fluorescent centers were recorded in the synovial fluid in diseased dogs compared with healthy dogs. The synovial fluid metabolic fingerprint of canine patients with medial compartment disease differed from that of healthy dogs. Our study demonstrated the feasibility of synovial fluid fingerprinting to identify disease-specific profiles of synovial fluid metabolites.

Early diagnosis of colorectal cancer in rats with DMH induced carcinogenesis by means of urine autofluorescence analysis.

Cancer is one of the most highlighted topics of current research. Early detection of this disease allows more effective therapy, hence higher chance of cure. Application of fluorescence spectral techniques into oncological diagnostic is one of the potential alternatives. Chemically induced carcinogenesis in rats is widely used model for exploration of various aspects of colorectal cancer. This study shows value of discriminate analysis of urine fluorescent fingerprint between healthy control group of rats and those with dimethylhydrazine induced early lesions of colorectal cancer. Using fluorescence spectroscopy, significant difference (P < 0.05) between both of group was achieved.

Hydroxybenzoic acids and their derivatives as peroxynitrite scavengers.

A social challenge of the 21(st) century is to reduce the incidence of chronic diseases. A balanced diet rich in polyphenols could contribute to reduce the risk and to the prevention of diabetes, coronary heart disease, cancer, Alzheimer's diseases and cataract(1). Hydroxybenzoic acids (HBA) and their derivatives, which are one of the substances responsible for these beneficial properties, are known mainly due to their antioxidant properties(2). They are effective scavengers of free radicals and reactive nitrogen species, such as peroxynitrite. Peroxynitrite is resulting from the reaction of nitric oxide with superoxide, causes lipid peroxidation and subsequent cellular damage and is responsible for the inactivation of many enzymes, activation of stress signalling pathways, release of proapoptotic factors, as well as cardiovascular dysfunction in septic schock(3). In this study we have tested 2-HBA, 3-HBA, 4-HBA, acetylsalicylic acid, 4-HBA methyl and propyl esters, 2,3-dihydroxybenzoic acid (DHBA), 2,5-DHBA, 2,4-DHBA, 2,6-DHBA, 3,5-DHBA, 3,4-DHBA, gallic acid and caffeic acid, by UV/VIS spectroscopy. The best ability to scavenge peroxynitrite was observed for gallic acid, 2,4-DHBA, 3,5-DHBA and caffeic acid. Improved comprehension of the complex relationship between the antioxidant properties of substances and their structure is important to understand their proper use in the prevention and treatment of diseases and for the detection of pathological processes. Monitoring and improved understanding of the antioxidant properties of hydroxybenzoic acid derivatives are important due to their frequent use in modern medical nutrition therapies.

Naturally occurring substances and their role in chemo-protective effects.

Cancer chemoprevention is defined as the use of natural, synthetic or biological chemical agents to reverse, suppress or prevent carcinogenic progression of invasive cancer. Carcinogenesis is a complex multi-step process; therefore, it is necessary to attack cell proliferation, stimulate apoptosis and inhibit angiogenesis. There have been more than 60 randomised trials using chemopreventive potential agents. The success of several recent clinical trials in preventing cancer in high-risk populations suggests that chemoprevention is a rational and appealing strategy. In this review, we describe the conceptual basis for the chemoprevention of cancer, proven concepts of efficiency and current trends in the use of chemopreventive agents according to place and mechanism of action. We classify chemopreventive substances into seven groups based on their chemical structure and their effects, namely, deltanoids (paracalcitriol), retinoids (13-cis retinoic acid), non-steroidal anti-rheumatics (Deguelin), antiestrogens (genistein), polyphenols (curcumin), sulphur containing compounds (sulforaphane) and terpenes (lycopene). Chemoprevention is one of several promising strategies for reducing the incidence of malignant tumours or helping to prolong the time before recurrence.