Assessment of interleukin 17A and 23 in the course of bladder cancer and selected benign urological diseases.

Several cytokines have been indicated to be significantly involved in urological diseases. Interleukin 17A (IL-17A) and interleukin 23 (IL-23) have recently received attention for their involvement in inflammatory diseases and cancers. The aim of the study was to show changes in the level of pro-inflammatory interleukins IL-17A and IL-23 in patients with bladder cancer (BC) and selected urological diseases. An important cognitive aspect was to study the interdependencies between the studied interleukins and to assess their diagnostic value for such diseases. The material for the study was urine sample from patients with BC, urinary tract infection (UTI), urolithiasis, benign prostatic hyperplasia (BPH), US (urethral stricture), which was compared to the urine sample of healthy people without urological disorders. Interleukin concentrations were measured by the immunoenzymatic method. The levels of IL-17A and IL-23 in the urine of patients with BC, UTI, BPH and US were significantly higher compared to the control group. Statistically significant differences were found in the level of both interleukins compared to the control group in all diseases except urolithiasis. IL-17A and IL-23 correlated with each other in patients with all urological diseases except urolithiasis. The results of the conducted studies showed that selected urological diseases changed the levels of IL-17A and IL-23 in the urine of patients. The observations made confirmed the participation of these interleukins in the course of the urological diseases, especially in BC, and allowed to classify them as potentially useful parameters for diagnostic purposes.

Hyper-glycemia and insulinemia induce morphological changes and modulate secretion of S100B, S100A8, amyloid ß 1-40 and amyloid ß 1-42, in a model of human dopaminergic neurons.

Glucose metabolism in neuronal tissue declines during neurodegenerative disorders in a progressive, region-specific, and disease-specific manner. Studies have shown that extracellular hyper-glycemia affects the functioning of adenosine triphosphate (ATP) sensitive potassium channels located in neurons and astrocytes. Also, hyper-insulinemia contributes to the formation and progression of Alzheimer's disease (AD) via competition with amyloid ß (Aß) for insulin-degrading enzyme. Aß disruption is phosphatidylinositol 3-kinase pathway dependent, and increased circulatory insulin concentrations lead to Aß accumulation. In 2008, based on assessment of brain glucose utilization disorders and insulin signaling disruptions, it was proposed that AD could be called "type III diabetes". Proteins from the S100 family are actively secreted during metabolic and oxidative stress, but their role in neuronal cells has yet to be clarified. However, it has been demonstrated that they act in a dose-dependent manner, which may be crucial in the modulation of glucose and insulin metabolism in the brain. The goal of this paper was to elucidate the association between high glucose and insulin concentrations with extra- and intracellular S100B and S100A8 proteins levels as well as the correlation with toxic (Aß42) and physiologic (Aß40) forms of Aß. Medium and high glucose concentrations mimicking pre-diabetic and diabetic state, caused statistically significant discharge of S100b and S100A8 protein to the extracellular compartment. Similar effect was observed after 50 nM insulin incubation. Furthermore, the correlation coefficient patterns between those proteins shows similar associations which highlights possible effective and modulating role of S100 family in the metabolic disturbances occurring in neuropathological disorders.

The relationship between interleukin-13 and angiogenin in patients with bladder cancer.

Participation of anti-inflammatory interleukin-13 (IL-13) in the process of carcinogenesis was well studied. Angiogenesis plays a key role in the process of tumour growth and metastasis. Higher expression of angiogenin (ANG) have been proven in many types of cancers. The aim of the study was to more fully understand the significance of plasma IL-13 as an immunomodulator and ANG as a stimulator of the angiogenesis process in patients with bladder cancer (BC) and to investigate the relationship between parameters. These parameters were examined in the group of BC patients and in subgroups of BC depending on clinical stage: non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC), histopathologic malignancy low grade (LG), high grade (HG) and in primary and recurrent BC. The level of IL-13 and ANG in the plasma of BC patients and controls were measured by enzyme-linked immunosorbent assay. All calculations were done using the STATISTICA 13.3 (TIBCO software Inc.). Plasma levels of IL-13 and ANG were significantly higher in BC patients and in all patient subgroups examined than in the controls (p < 0.001). A negative significant correlation was found between ANG and IL-13 levels in BC-patients. Based on the receiver operating characteristic curves (ROC), IL-13 had good diagnostic value in BC. The presented results may suggest a relationship between angiogenesis and inflammation in the pathogenesis of bladder cancer and the development of this disease. With the increase of IL-13 level in BC-patients plasma, the ANG level decreased.

Investigation of seminal plasma chitotriosidase-1 and leukocyte elastase as potential markers for 'silent' inflammation of the reproductive tract of the infertile male - a pilot study.

Inflammatory mediators - chitotriosidase-1 (CHIT1) and leukocyte elastase (LE) - were analyzed in human seminal plasma in relation to total antioxidative status (TAS) and pro-inflammatory markers IL-1ß and IL-6. Samples collected from 34 males who were part of infertile couples were divided into normozoospermic (N; n = 12, without symptoms of inflammation), oligozoospermic (O; n = 11) and teratozoospermic (T; n = 11) groups. significant differences were observed only in CHIT1 concentration between N and O samples. However, a higher mean LE concentration was also observed in O and T patients (3.7-times and 900-times, respectively) compared with the N group. in IL-1ß and IL-6 concentrations, an upward trend was observed from N, through O, up to the T group. The positive correlation between the concentration of IL-1ß and the activity and specific activity of CHIT11 as well as the moderate negative correlation between concentrations of IL-1ß and CHIT1 may suggest that elevated CHIT11 levels appeared in early stages of inflammation before the increase in IL-1ß concentrations, or remained stable even after the levels of cytokine decreased. The above seem to confirm the role of CHIT1 in the manifestation of 'silent' inflammation at a very early stage. To conclude, CHIT1 concentration appears to be an interesting biomarker that signals the presence of possible 'silent' inflammation accompanying oligozoospermia. We cannot draw such conclusions regarding LE concentration, because, although we observed differences in the mean values and medians between analyzed groups, they were not significant. The utility of CHIT1 in the follow-up of oligozoospermia-associated 'silent' subclinical inflammation is promising, but further studies on a larger patient test set are required.

Extracellular signal-regulated kinases, P38 and c-Jun N-terminal kinases phosphorylation changes in PC12 cells with diabetic disturbances and comorbid excitotoxicity - a preliminary report.

Phosphorylation of amino acid residues of extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinases (JNK) contributes to the initiation of complex pathways of intracellular signal transduction, which play a role in the development of excitotoxicity, which is important in pathogenesis both in diabetes and neurodegeneration. Due to reports on the relationship between these two diseases, it is important to explore pathways in the coexistence of both of them. This study investigated ERK, p38 and JNK protein kinases phosphorylation changes in diabetic in vitro conditions with accompanying excitotoxicity reflected by high L-glutamate concentrations. An InstantOne ELISA test in cell lysates was performed to evaluate the intensity of phosphorylation of ERK, p38 and JNK occurring as a result of the incubation of undifferentiated PC12 cells with solutions of glucose (G1,G2), insulin (I1,I2) and L-glutamate (L1,L2). We observed increased phosphorylation of JNK (Thr183/Tyr185) and p38 (Thr180/Tyr182) kinases. For both these kinases, we have shown an increase in phosphorylation in case of double combinations for the following reagents: G1I1, G1I2, G2I1, G2I2, G2L1, I2L2 and the triple ones: G1I2L1 and G2I1L2. The research based on the analysis of selected protein kinases under diabetic conditions with accompanying excitotoxicity, represents an important cognitive issue for research on neurodegenerative disorders resulting from long-term type 2 diabetes. The confirmed changes in protein phosphorylation of p38 and JNK kinases suggests changes in the conformation and activity of these proteins under conditions of increased excitotoxicity resulting from diabetes.

The impact of metalloestrogens on the physiology of male reproductive health as a current problem of the XXI century.

In the XXIst century in highly developed countries, progressively decreasing male reproductive potential is indicated. In recent years epidemiological studies indicate the deterioration of semen parameters: reduction of ejaculate volume, sperm count, and mobility, as well as abnormalities in their morphology. Male infertility can result from many different agents, such as: anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies and lifestyle (especially obesity, heat and tobacco smoking). It is well documented that adverse changes in male fertility also seem to be associated with environmental exposure to different substances, especially endocrine active factors, known as xenoestrogens, and among these metal ions, known as metalloestrogens, are very important. The role of some metalloestrogens in various diseases, both in women and men, is known and particularly well-proven in women, but still little is known about their role in the regulation of male reproductive potential. Thus we decided to analyse the available information exploring this problem. The review was carried out using the Medline and Google Scholar databases, using the keywords: xenoestrogens, metalloestrogens, male fertility, semen quality, male reproductive potential, mechanisms of metalloestrogen action, environmental pollution and the name of the particular metal. Articles published between 2000 - 2019 have been taken into account, including human and vertebrate animal studies and cell lines. The aim of this review is to discuss the role and mechanisms of action of fifteen metalloestrogens in the human organism, as well as in animal models, and cell cultures, paying special attention to their influence on the physiology of male reproductive health, according to the current state of knowledge. The role of certain metals in human reproduction is still poorly investigated and for some of them only single studies are available. Many factors in our daily lives have a significant impact on male fertility, therefore education is necessary on the threats and how they may be eliminated as far as possible.

Crucial players in Alzheimer's disease and diabetes mellitus: Friends or foes?

Alzheimer's disease (AD) and diabetes mellitus, especially type 2 (T2DM), are very common and widespread diseases in contemporary societies, and their incidence is steadily on the increase. T2DM is a multiple metabolic disorder, with several mechanisms including hyperglycaemia, insulin resistance, insulin receptor and insulin growth factor disturbances, glucose toxicity, formation of advanced glycation end products (AGEs) and the activity of their receptors. AD is the most common form of dementia, characterized by the accumulation of extracellular beta amyloid peptide aggregates and intracellular hyper-phosphorylated tau proteins, which are thought to drive and/or accelerate inflammatory and oxidative stress processes leading to neurodegeneration. The aim of this paper is to provide a comprehensive review of the evidence linking T2DM to the onset and development of AD and highlight the unknown or poorly studied "nooks and crannies" of this interesting relationship, hence providing an opportunity to stimulate new ideas for the analysis of comorbidities between AD and DM. Despite, indication of possible biomarkers of early diagnosis of T2DM and AD, this review is also an attempt to answer the question as to whether the crucial factors in the development of both conditions support the link between DM and AD.

Preliminary Evaluation of the Diagnostic Usefulness of Uroplakin 2 with an Assessment of the Antioxidant Potential of Patients with Bladder Cancer.

BACKGROUND: Urothelial carcinoma is the most common type of bladder cancer (BC). It makes up more than 90% of all bladder cancers. Uroplakins are tissue-specific, glycoproteins, playing a role in the construction and function of urothelium. The emergence of uroplakins in the urine and/or plasma may be of potential importance in the early detection of BC. In our study, the diagnostic value of plasma and urine uroplakin 2 (UP2) concentration in bladder cancer was investigated, with an assessment of the antioxidant potential of BC patients. The correlation between UP2, total antioxidant capacity (TAC), and concentration of glutathione (GSH) was also examined. MATERIALS AND METHODS: This study included 61 BC patients and 33 healthy controls. UP2 concentration was estimated by the immunoenzymatic method (ELISA). TAC and GSH were determined in spectrophotometrically methods. RESULTS: UP2 concentration in BC patients was significantly higher (p≤0.001) both in plasma and in urine compared to the control groups (C). TAC concentration in urine (p≤0.001) and GSH concentration in plasma (p=0.047) were significantly lower in BC group compared to the C group. The high specificity and sensitivity for UPK2 in plasma (76%, 80%, respectively) and urine (88%, 84%, respectively) were observed. Positive correlations were observed between concentration of UP2 in plasma and TAC concentration in urine and between UP2 concentration in plasma and GSH concentration in the same material. CONCLUSION: The study showed the early diagnostic value of urine and plasma UP2 in BC. There was a decrease in UP2 concentration in the urine of patients with the development of BC. The decrease of antioxidant systems (TAC, GSH) indicates their relationship with the BC process. Based on the obtained results, it is justified to continue the study in a larger group of patients with BC.

Melatonin, advanced oxidation protein products and total antioxidant capacity as seminal parameters of prooxidant-antioxidant balance and their connection with expression of metalloproteinases in context of male fertility.

Currently, in highly developed, industrialized countries male factors are identified as the primary cause of infertility in about 60% of childless couples. Standard semen analysis parameters, such as sperm morphology, number and motility, are important in predicting the fertility of large populations, but they are not sufficient to fully specify a particular donor sperm's ability to fertilize the egg. The semen also comprises components, which may also affect sperm fertilizing ability and which have thus far remained little explored: the biochemical parameters of the seminal plasma secreted by the testis, the seminiferous tubules and the prostate gland, such as: matrix metalloproteinases (MMP-2 and MMP-9) and their specific tissue inhibitors (TIMP-1 and TIMP-2). We highlight the need for a better determination of prooxidant-antioxidant balance parameters such as: melatonin, advanced oxidation protein products (AOPPs) and total antioxidant capacity (TAC) in human semen when establishing the diagnostics of male subfertility or infertility. We also discuss their connection with seminal plasma metalloproteinases and their inhibitors. In particular, we believe that the cumulative and synergic effects of the sperm redox parameters on male fertility need to be better explored and we suggest that they should be studied in conjunction with other biologically active parameters of the ejaculate such as the expression of metalloproteinases and their tissue inhibitors. This will enable a better understanding of how their correlated effects impact semen condition.

Hemoglobin - a novel ligand of hepatocyte ectopic F1-ATPase.

The liver is largely responsible for free hemoglobin uptake, but the molecular mechanism of this phenomenon has never been revealed. This paper presents the results of the study on hemoglobin binding components of the hepatocyte membrane that were purified using affinity chromatography on a hemoglobin matrix and identified by peptide mass fingerprinting. Both F1-ATPase alpha and beta subunits were retrieved. The binding was confirmed via an intrinsic fluorescence quenching study using a purified recombinant F1-ATPase beta subunit, and the dissociation constant for the complex was estimated from the saturation binding curve (Kd = 7.5 x 10(-7) M). The results indicate that haemoglobin binds to hepatocyte ectopic F1-ATPase. We suggested the plausible role of the receptor in endocytosis of haemoglobin by the hepatocyte.

Oxidatively modified forms of albumin in patients with risk factors of metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a complex metabolic disease connected especially with lipid and carbohydrate disturbances. It is postulated that oxidative stress (OS) is linked to metabolic syndrome, constituting a novel component of its pathogenesis. AIM: We aimed to examine the plasma level of oxidatively modified proteins--advanced oxidation protein products (AOPP) and ischemia modified albumin (IMA)--as well as thiol (SH) groups and evaluate their connection with metabolic agents in relation to MetS prevalence. SUBJECTS AND METHODS: The levels of AOPP, IMA and SH groups were measured spectrophotometrically in 106 patients with MetS risk factors and in 32 control subjects. RESULTS: The levels of examined parameters differed significantly between patients with MetS risk factors and the control group. AOPP significantly correlated with glucose (r = 0.30, p = 0.008), HDL-Ch (r = -0.34, p = 0.005), TG (r = 0.48, p < 0.001) and fibrinogen (r = 0.37, p < 0.001). The levels of AOPP and IMA increased progressively with the number of MetS risk factors, being the most significant for AOPP. The highest values of AOPP were associated with the presence of at least three risk factors. Only AOPP were an independent determinant for MetS occurrence in the studied population (OR = 2.72, p = 0.04). Mutual dependence between metabolic, oxidative stress and inflammatory parameters was revealed. CONCLUSIONS: Oxidative modifications of proteins are increased in MetS and accumulation of MetS risk factors enhances manifestation of OS. AOPP is the most appropriate parameter for determination of OS, with potential diagnostic value in MetS patients.

Markers of oxidative protein damage in plasma and urine of type 2 diabetic patients.

This study aims to measure selected markers of oxidative protein damage (OPD) in patients with type 2 diabetes mellitus (T2DM) in order to estimate their utility as indicators of oxidative stress (OS) and to search for possible associations between them. The concentrations of advanced oxidation protein products (AOPP) and total sulphydryl (TSH) and reactive carbonyl (RCO) groups are measured in the plasma (P) and urine (U) of 60 patients and 22 controls using spectrophotometric methods. Significantly higher plasma concentrations of AOPP (P < 0.001), RCO groups (P < 0.01) and their P/U indexes (P < 0.001) as well as urinary levels of the RCO and TSH groups (P < 0.001) were observed in the diabetic patients compared with the controls. In contrast, the plasma levels and P/U index of the TSH groups were significantly lower (P < 0.001). A progressive increase in AOPP (plasma, urine and P/U index) in the course of albuminuria was noted, but significant differences among the subgroups of patients (with normoalbuminuria, microalbuminuria and macroalbuminuria) were found only in plasma. Plasma levels of all the measured parameters of OPD showed significant changes in T2DM patients compared with the control group. The largest increase was observed for AOPP. As the urinary AOPP concentration was not significantly different to that of the controls, it cannot be recommended as a marker of oxidative stress for monitoring the development of diabetic nephropathy. The P/U indexes did not provide any more information than the plasma concentrations of the studied markers.

[Cystatin C as a marker of glomerular filtration rate]. / Cystatyna C jako wskaznik przesaczania klebuszkowego nerek.

The assessment of the glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin C, a cysteine protease inhibitor, which can be measured by light scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. This paper reviews so far obtained results dealing with cystatin C measurement, reference intervals and its diagnostic significance in nephropathy. Although serum cystatin C can generally be recommended as a marker of GFR, especially to detect mild GFR reductions, further clinical studies should be performed to confirm the validate in renal transplants and cancer patients.

Concentration of leukocyte elastase in plasma and polymorphonuclear neutrophil extracts in type 2 diabetes.

The concentration of leukocyte elastase/alpha1-proteinase inhibitor complexes in plasma and polymorphonuclear neutrophil extracts, and plasma trypsin inhibitory capacity were determined in 88 patients with type 2 diabetes and 47 control subjects. Higher values of these variables were found in patients as compared to controls (p < 0.001). The concentration of elastase was higher in obese patients than in lean ones (p < 0.05 for plasma, p < 0.01 for polymorphonuclear leukocytes). Only leukocyte elastase levels were significantly higher in the group with both micro- and macroangiopathy in comparison to the group with microangiopathy (p < 0.01) or macroangiopathy (p < 0.05) alone. Poor short-term glycaemic control was associated with higher elastase concentration in plasma and neutrophils (p < 0.05). The present study demonstrates that measurements of plasma polymorphonuclear neutrophil elastase level can be considered as a marker of development of diabetic angiopathy.

[Levels of cystatin C, activity of antipapain and antitrypsin in plasma of patients with diabetes mellitus type 2]. / Stezenie cystatyny C, aktywnosc antypapainowa i antytrypsynowa osocza krwi u chorych na cukrzyce typu 2.

In plasma of 72 patients with diabetes mellitus type 2, cystatin C concentration, the antipapain as well as antitrypsin activities were determined. Statistically significant increase of levels of all the examined parameters (higher for inhibitors of cysteine proteases) was found in comparison to healthy persons. When considering types of vascular complications, the highest concentration of cystatin C and the strongest positive correlation with antipapain activity was found in the group of patients with microangiopathy. It might be connected with glomerular damages. Only antipapain as well as antitrypsin activities showed significant correlation with glycaemic control as measurement by glycated haemoglobin concentration.

Plasma cystatin C concentration in non-insulin-dependent diabetes mellitus: relation with nephropathy.

We determined plasma concentrations of cystatin C, beta2-microglobulin - beta2-MG (low molecular mass protein markers of glomerular filtration rate - GFR), creatinine (marker of GFR) and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion (marker of glomerular and tubular dysfunction) in 41 non-insulin-dependent diabetic patients. A significant increase of all the measured parameters (p<0.001, p<0.05, p<0.05 and p<0.001, respectively) in comparison to the control group, was observed. In the patients with microalbuminuria, only plasma cystatin C concentration and urinary NAG excretion increased significantly in comparison to patients with normoalbuminuria. At a cut-off level of 1.74 mg/l for cystatin C and 1.81 U/g creatinine for NAG (95% percentile of the normoalbuminuric group), the sensitivity of the tests for detecting microalbuminuria was 82% for cystatin C and 86% for NAG. The specificities were 88 and 92%, respectively. The present study demonstrated that determination of plasma cystatin C might be useful in the detection of incipient diabetic nephropathy and is a potentially better marker than creatinine or beta2-MG. No correlation between parameters measured in plasma or urine and glycated hemoglobin was found.

[Contents of glycogen in neutrophils in patients with diabetes]. / Zawartosc glikogenu w granulocytach obojetnochlonnych chorych na cukrzyce.

Glycogen neutrophils level was evaluated in 54 patients with non-insulin dependent diabetes mellitus (NIDDM) and 10 patients with insulin dependent diabetes mellitus (IDDM). Glycogen concentration estimated by histochemical method was lower in diabetics than in control group. Patients with NIDDM were divided in the groups according to: sex, duration of disease, a kind of complications and a way of treatment. The glycogen contents in neutrophils, defined in "score"-unit was not different in isolated groups. There was found significant correlation between glycogen contents in neutrophils and the metabolic control in patients with IDDM (r = 0.72) and less significant in patients with NIDDM (r = 0.29).