Publications by authors named "Maria Warwas"

28 Publications

  • Page 1 of 1

[Glycated albumin as a marker of glycemia in diabetes and its vascular complications].

Postepy Hig Med Dosw (Online) 2015 May 17;69:638-48. Epub 2015 May 17.

Katedra i Zakład Biochemii Farmaceutycznej, Wydział Farmaceutyczny z Oddziałem Analityki Medycznej, Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu.

Effective glycemic control is very important to prevent the onset and the progression of chronic complications in diabetic patients. It is known that glycation of various proteins is increased in diabetic patients compared with non-diabetics. Among these glycated proteins, glycated hemoglobin (HbA1c) is commonly used as a gold standard index of glycemic control in the clinical setting. However, it can be unreliable in conditions affecting the lifespan of erythrocytes (120 days) as well as in the clinical state in which glycemic control alleviates or deteriorates in a short period. By overcoming the shortcomings of HbA1c, glycated albumin (GA) has gained interest as a useful index for an intermediate glycation period (2 weeks) and pathogenic protein. After giving a brief overview of the key role of HbA1c as a long-term glycemic marker, this review focuses on (a) glycation of human albumin and its main properties, (b) methods of GA determination, (c) the recent clinical status of GA as a glycemic index in diabetic patients and its association with vascular complications. Finally, conditions with a possible inaccurate GA level are also mentioned.
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http://dx.doi.org/10.5604/17322693.1153082DOI Listing
May 2015

Activities of neutrophil membrane-bound proteases in type 2 diabetic patients.

Arch Med Res 2014 Jan 5;45(1):36-43. Epub 2013 Dec 5.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wroclaw, Poland.

Background And Aims: Hyperglycemia and oxidative stress in type 2 diabetes (T2DM) provoke neutrophil overstimulation and the release and/or translocation of proteases from granules to the cell surface. Although the expression of neutrophil membrane-bound elastase (MLE) is well documented, the presence of the membrane-bound form of cathepsin B (MCB) is unknown. The aim of our study was to evaluate the neutrophil MLE and MCB activities in T2DM patients and their associations with the metabolic and clinical parameters of the disease.

Methods: Neutrophils were obtained from 47 T2DM patients and 20 control subjects. The activities of MLE and MCB and the intracellular activities of the examined proteases (ILE and ICB, respectively) were measured using fluorometric substrates. Additionally, the percentage equivalents of the activities, namely, MLEtot/ILEtot and MCBtot/ICBtot, were calculated. The susceptibility to inhibitors of both forms of the studied proteases was also determined.

Results: A significant increase in the activities of MLE, MCB, ILE, and ICB was found in neutrophils from T2DM patients compared with the control group. The percentage equivalent (contribution of the total membrane-bound activities to the total intracellular activities) was also higher. A partial resistance of the membrane-bound forms toward their inhibitors was revealed. Higher activities of both the membrane-bound and the intracellular proteases were also observed in patients with poor glycemic and metabolic control. The differences between subgroups with different therapeutic schemes were also revealed.

Conclusions: The pathophysiological implications of the neutrophil membrane-bound forms of leukocyte elastase and cathepsin B are of great importance in the development of T2DM and its complications.
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http://dx.doi.org/10.1016/j.arcmed.2013.10.003DOI Listing
January 2014

Influence of aminoglycoside antibiotics on chicken cystatin binding to renal brush-border membranes.

J Pharm Pharmacol 2013 Jul 19;65(7):988-94. Epub 2013 Mar 19.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wrocław, Poland.

Objectives: Drug-induced kidney injury is a serious adverse event which needs to be monitored during aminoglycoside therapy. Urine cystatin C is considered an early and sensitive marker of nephrotoxicity. Cystatin C, a low-molecular-weight serum protein, and basic drugs have a common transport system expressed in the apical membrane of renal proximal tubular cells. The aim of this study was to investigate whether aminoglycoside antibiotics influenced cystatin C binding to the renal brush-border membrane.

Methods: The binding study was performed using a rapid filtration technique and affinity column displacement method.

Key Findings: Concentration-dependent inhibition of chicken cystatin binding to brush-border membranes by gentamicin was observed. The gentamicin interaction with brush-border membranes was of relatively low affinity (Ki = 32 μm) in comparison with the chicken cystatin affinity to the binding sites (Kd = 3.6 μm). Amikacin and gentamicin were only able to displace chicken cystatin from the chromatographic affinity column in concentrations several times higher than normally found in the tubular fluid during standard aminoglycoside therapy.

Conclusion: Cystatin reabsorption in the proximal tubule cannot be significantly affected by aminoglycoside antibiotics because of their relatively low affinity to common binding sites on the brush-border membrane.
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http://dx.doi.org/10.1111/jphp.12058DOI Listing
July 2013

Binding of glycated ovocystatin to rat renal brush border membranes.

Anim Sci J 2013 Oct 18;84(10):702-7. Epub 2013 Apr 18.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wroclaw, Poland.

Glycated proteins are considered as one of the factors involved in the pathogenesis of diabetic complications, including nephropathy. These proteins are formed endogenously under conditions of hyperglycemia, as well as being provided with food containing sugars, which was subjected to high temperature. Examples are egg products. One of the proteins found in eggs in a relatively high concentration is chicken cystatin (ovocystatin). It is now believed that some proteins can passage the intestinal epithelium by transcytosis directly into the bloodstream. Thus, glycated protein present in food can be an additional source of glycotoxins. The aim of this study was to compare the affinity of native and glycated cystatin to the brush border membranes of rat kidney. Kinetic analysis was performed with surface plasmon resonance technique using sensor chip L1. Dissociation constants for native and glycated cystatin (Kd ) were 2.76 μmol/L and 3.82 μmol/L, respectively. The results of our study indicate that glycation only slightly affects binding of cystatin to brush border membranes. This suggests that glycated cystatin and other glycated proteins may also be efficiently taken up in the kidney proximal tubule. The observation may be important for understanding the mechanisms involved in the development of diabetic nephropathy.
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http://dx.doi.org/10.1111/asj.12060DOI Listing
October 2013

Ischemia-modified albumin (IMA) is increased in patients with chronic hepatitis C infection and related to markers of oxidative stress and inflammation.

Acta Biochim Pol 2012 6;59(4):661-7. Epub 2012 Dec 6.

Department of Pharmaceutical Biochemistry, Wrocław Medical University, Wrocław, Poland.

Inflammation and oxidative stress have been reported in patients with chronic hepatitis C (CHC) infection, but their influence on ischemia-modified albumin (IMA) levels and diabetes prevalence remains unknown. Sixty-three CHC patients, 28 with diabetes, and 40 healthy controls were enrolled in the study. Circulating levels of oxidative stress markers [Nε-(carboxymethyl)lysine- advanced glycation end products (CML-AGEs) and advanced oxidation protein products-(AOPPs)], pro-inflammatory cytokines (interleukin-6, and tumor necrosis factor α), and high-sensitivity C-reactive protein (hsCRP) were assessed. Compared with the controls, the CHC patients with diabetes showed a significant increase in plasma concentrations of IMA, AOPPs, interleukin-6 and hsCRP (P < 0.05). The values of IMA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were found between hsCRP and presence of diabetes, IMA (both P < 0.01) and AOPP levels (P < 0.05). CML-AGEs did not show any significant correlation with IMA, markers of inflammation and presence of diabetes. In conclusion, we have documented significant elevation in plasma levels of IMA and AOPPs in CHC patients. In addition, circulating IMA was associated with inflammation markers and diabetes prevalence. This observation suggests a relationship between IMA and inflammation in CHC patients with diabetes, which may represent one of the mechanisms involved in the accelerated atherosclerosis in this population.
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June 2013

Picolinic acid in patients with chronic hepatitis C infection: a preliminary report.

Mediators Inflamm 2012 10;2012:762863. Epub 2012 Apr 10.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland.

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients.
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http://dx.doi.org/10.1155/2012/762863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368595PMC
September 2012

[Serum chitotriosidase activity as a biomarker of pulmonary sarcoidosis].

Pol Merkur Lekarski 2011 Sep;31(183):179-82

Department of Pharmaceutical Biochemistry, Medical University of Wrocław, Poland.

Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology, which is characterized by a variable clinical presentation and course. The diagnosis of this disease is usually supported by the three elements: compatible clinical and radiologic findings, tissue biopsy specimen that reveals noncaseating epithelioid granulomas and the absence of known granulomagenic agent. During the last years the new diagnostic methods have been discovered, but serum markers of the sarcoidosis are still under studying. Among the potential markers of sarcoidosis, a recently proposed indicator is chitotriosidase, a chitinase produced by chronically activated macrophages. The review of the literature showed that chitotriosidase activity is only a surrogate biomarker to confirm diagnosis, but is a useful marker for disease activity monitoring and prognosis. The correlation with the radiological stages of disease suggest that determination of chitotriosidase activity could decrease the number of X-ray examination.
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September 2011

[Urinary cystatin C as a biomarker of renal tubular injury].

Postepy Hig Med Dosw (Online) 2011 Sep 2;65:562-8. Epub 2011 Sep 2.

Katedra i Zakład Biochemii Farmaceutycznej Akademii Medycznej we Wrocławiu.

Cystatin C (cysC) is an endogenous cysteine peptidase (proteinase) inhibitor that has been intensively investigated as a biomarker of kidney function for many years. It is freely filtered at the kidney glomerulus because of its small size and lack of cysC binding protein. A very small amount of cysC appears in the urine because of its total reabsorption in the proximal tubule and lack of secretion. Since 1985 cystatin C has been studied mainly in serum/plasma as an alternative biomarker to serum creatinine to estimate GFR. In this review we present the recent discoveries concerning urinary cystatin C determination as a tubular injury biomarker.
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http://dx.doi.org/10.5604/17322693.957690DOI Listing
September 2011

Advanced oxidation protein products and inflammatory markers in liver cirrhosis: a comparison between alcohol-related and HCV-related cirrhosis.

Acta Biochim Pol 2011 14;58(1):59-65. Epub 2011 Mar 14.

Department of Pharmaceutical Biochemistry, Liver Diseases and Acquired Immune Deficiency, Wrocław Medical University, Wrocław, Poland.

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.
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July 2011

Comparison of the usefulness of plasma levels of oxidatively modified forms of albumin in estimating kidney dysfunction in diabetic patients.

Clin Invest Med 2010 Apr 1;33(2):E109. Epub 2010 Apr 1.

Department of Pharmaceutical Biochemistry of Wroclaw Medical University, 50-139 Wrocław, Poland.

Purpose: Advanced oxidation protein products (AOPP) and ischemia-modified albumin (IMA) are forms of oxidatidatively modified albumin and have recently been investigated as indicators of oxidative stress. They are increased in different disorders, including diabetes mellitus, as a result of hyperglycaemia, oxidative stress and hypoxia. The usefulness of the plasma levels of these two parameters in estimating kidney dysfunction in type 2 diabetic patients (T2DM) was compared in this study.

Methods: Plasma levels of AOPP and IMA were determined spectrophotometrically in 218 individuals, 153 patients with T2DM and 65 healthy people.. The urinary albumin/creatinine ratio (UACR) was used as the reference to define the stage of kidney dysfunction by the assessment of the degree of albuminuria.

Results: Receiver Operating Characteristic (ROC) curve analysis, likelihood ratio (LR), and Youden's index (J) revealed that AOPP and IMA had acceptable sensitivities and specificities in individuals with different degrees of albuminuria; however, AOPP had higher values of the area under the curve (AUC: 0.934) than IMA, as well as 100% sensitivity and 77.01% specificity for distinguishing patients with micro- and macroalbuminuria.

Conclusions: Both AOPP and IMA may be helpful clinical markers for estimating kidney dysfunction, but AOPP is better able to identify diabetic patients with nephropathy. We suggest that AOPP is almost ideal for discriminating between T2DM patients with micro- and macroalbuminuria.
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http://dx.doi.org/10.25011/cim.v33i2.12349DOI Listing
April 2010

Elevated advanced oxidation protein products levels in patients with liver cirrhosis.

Acta Biochim Pol 2009 9;56(4):679-85. Epub 2009 Dec 9.

Department of Pharmaceutical Biochemistry, Wrocław Medical University, Wrocław, Poland.

Serum concentrations of advanced oxidation protein products (AOPPs) and glycation end products (AGEs) were assessed with respect to functional compromise of liver, as determined by the Child-Pugh and MELD scores. Patients with decompensated liver cirrhosis (Child-Pugh B and C) exhibited significantly higher serum concentrations of AOPPs than both patients with compensated liver cirrhosis (Child-Pugh A) and controls. The levels of plasma AGEs in all liver cirrhotic patients were higher when compared with those with the controls and this difference was statistically significant. Plasma total antioxidant status of the patients was significantly lower than that of controls. Significant positive correlations between AOPPs level and the MELD score and between the oxidative stress index and the MELD score were found in all patients with liver cirrhosis. Altered AOPPs levels in decompensated patients may influence the potency of oxidative stress and the progression of liver disease.
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February 2010

[Serum activity of chitotriosidase, lysozyme and cathepsin H in patients with lung cancer and patients with inflammatory exudate (preliminary report)].

Pol Merkur Lekarski 2009 Mar;26(153):194-7

Department of Pharmaceutical Biochemistry, Medical University of Wroclaw, Poland.

Unlabelled: Lung cancer remains the leading cause of cancer death over the world. Although new diagnostic methods have been discovered, new biomarkers of the cancer are still under studying. A human chitinolytic enzyme called chitotriosidase hydrolyzes chitin and chitotrioside substrates. It is specifically expressed by activating macrophages and seems to play a role in the defense against chitinous human pathogens. Recently it has been shown that chitotriosidase may also attend to the inflammatory process. The aim of the study was to determine chitotriosidase activity in serum of patients with lung cancer and patients with inflammatory exudate. We studied the usefulness of the above parameter determination in differentiation between lung cancer and inflammation. In addition, serum activity of lysozyme and cathepsin H was determined.

Materials And Methods: The study included 17 patients with inflammatory pleural exudate--group 1., 40 lung cancer patients with malignant pleural effusion--group 2. and 37 healthy subjects. All the patients of group 2. were divided into 2 subgroups: 2A without metastases (n = 23) and 2B with metastases (n = 17). Chitotriosidase and cathepsin H activity was determined in serum by a fluorometric methods. Serum lysozyme activity was measured by turbidimetric method with Micrococcus luteus as substrate.

Results: We observed an increase of the chitotriosidase activity in serum patients of both studied group in comparison with the control. The activity of the chitotriosidase in lung cancer patients was significantly higher than in the control (36.7 vs 68.1 nmol/ml/h; p < 0.01). There were no significant differences in serum lysozyme and cathepsin H activity in patients in comparison to healthy subjects.

Conclusion: The results suggest that activity of the chitotriosidase can not be used to differentiation between inflammation and cancer in lung.
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March 2009

[Oxidative stress and endothelium dysfunction in diabetes mellitus type 2].

Pol Merkur Lekarski 2008 Aug;25(146):120-3

Akademia Medyczna we Wrocdawiu, Katedra i Zakład Biochemii Farmaceutycznej.

Unlabelled: The aim of our study was to estimate the influence of oxidative stress on the function of vascular endothelium in diabetes mellitus type 2, through the measurement plasma levels of chosen parameters reflecting these disturbances--concentration of advanced oxidation protein products (AOPP) and activity of gamma glutamyltransferase (GGT) and N-acetyl-beta-glucosaminidase (NAG).

Materials And Methods: 73 patients with type 2 diabetes mellitus and 23 healthy people, which made up the control group were examined. In plasma of these subjects concentration of AOPP by spectrophotometric method with the use of potassium iodide; activity of GGT by spectrophotometric method and NAG activity by spectrofluorymetric method were determined.

Results: The plasma levels of all examined parameters were significantly higher in diabetic patients than in healthy people. We observed increase of these parameters in groups of patients clustered on the basis of disease duration, glicemic state of diabetes and vascular area occupied by diabetic complication. The most significant changes in AOPP concentration were observed. There was statistically significant correlation between AOPP and GGT, however there was no any direct connection of these two parameters with NAG activity.

Conclusions: We showed significantly increase in the AOPP concentration and activities of GGT and NAG in plasma of patients with type 2 diabetes, which was induced by hyperglycemia and oxidative stress connected with this disease. The growth of examined parameters had no direct connection with each other, however was connected with chronic nature of this disease, glycemic decomposition and vascular area occupied by diabetic complication.
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August 2008

[Fluorescence of age in serum in detecting liver cirrhosis and hepatocellular carcinoma among patients with anti-HCV antibodies].

Przegl Epidemiol 2008 ;62(2):393-400

Katedra i Zakład Biochemii Farmaceutycznej AM we Wrocławiu.

Objective: To evaluate usefulness of total fluorescence of advanced glycation end products (AGE) and haptoglobin (Hp) measurement in human serum as parameters in liver cirrhosis and hepatocellular carcinoma development among patients with anti-HCV antibodies.

Materials And Methods: 43 patients (20 women and 23 men) with chronic hepatitis HCV were examined (14 individuals with liver cirrhosis and 9 with primary liver cancer). The control group numbers 20. As reflection of AGE concentration, total fluorescence in serum samples was measured with spectrofluorimetric method and haptoglobin with microplate guaiacol test.

Results: We affirmed that total fluorescence in examined groups was higher than in healthy subjects, but increase was not statistically significant. Fluorescence of AGE in serum from patients with hepatocellular carcinoma was lower in comparison to patients with cirrhosis and anti-HCV carriers. Haptoglobin was significantly decreased in serum of cirrhosis patients as compared to HCV carriers of patients with hepatocellular carcinoma (p < 0.001).

Conclusions: The measurement of total fluorescence AGE is not differentiating for liver cirrhosis and hepatocellular carcinoma among anty-HCV carriers. We confirmed that haptoglobin, parameter included in fibrotest, is very useful, in detecting liver cirrhosis.
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November 2008

Ischemia-modified albumin level in type 2 diabetes mellitus - Preliminary report.

Dis Markers 2008 ;24(6):311-7

Department of Pharmaceutical Biochemistry of Wroclaw Medical University, Wrocław, Poland.

Aim: The main goal of the present study was the evaluation of ischemia-modified albumin (IMA) in patients with type 2 diabetes mellitus and estimation of its connection with vascular complications, glycemic control, hypertension, dyslipidemia and obesity.

Methods: In 76 diabetic patients and 25 control subjects, a plasma level of IMA by manually performed, spectrophotometric Co(II)-albumin binding assay was determined. Other parameters such as glucose, fructosamine, HbA_{1c}, total cholesterol and its fractions (HDL, LDL), triglicerydes were estimated by routine methods.

Results: Diabetic patients had significantly higher level of IMA in comparison with control subjects. There were not significant differences between groups with various states of vascular complications although the lowest concentration of IMA was observed in patients with microangiopathy. Patients with poor glycemic control had higher IMA level in comparison with these with good glycemic control. Significant correlation was observed between IMA and HbA_{1c}. Among the risk factors, only blood pressure and LDL showed a weak relationship with IMA level.

Conclusions: Our results revealed, for the first time, higher level of IMA in diabetic patients which confirms that it may be of non-cardiac origin. We can suggest that the albumin molecule in plasma of diabetic patients is modified in the chronic hypoxia conditions provoked mainly by hyperglycemia and oxidative stress in diabetes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850615PMC
http://dx.doi.org/10.1155/2008/784313DOI Listing
October 2008

Plasma glycooxidation protein products in type 2 diabetic patients with nephropathy.

Diabetes Metab Res Rev 2008 Oct;24(7):549-53

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland.

Background: In diabetes mellitus, hyperglycaemia accelerates non-enzymatic glycation and oxidative stress leading to damage of macromolecules, among others proteins. This manifests in the increased levels of advanced glycation end products (AGE) and advanced oxidation protein products (AOPP).

Objectives: To assess the plasma levels of AGE and AOPP in the patients with type 2 diabetes mellitus (T2DM) and to estimate its relation and connection with the degree of nephropathy.

Material And Methods: In 121 diabetic patients and 22 healthy people plasma levels of AGE and AOPP were determined with fluorimetric and spectrophotometric methods, respectively. To estimate nephropathy stage, albumin/creatinine ratio was calculated on the basis of albumin and creatinine concentrations in early morning urine samples.

Results: Diabetic patients had significantly higher levels of AGE and AOPP in comparison to healthy people. Both parameters were increasing progressively from normoalbuminuria, through microalbuminuria to macroalbuminuria. Statistically, the most significant differences were observed in AOPP concentration between separated groups. AGE fluorescence was significantly different on the same low, statistical level between patients with normoalbuminuria when compared to those with micro- and macroalbuminuria. Plasma AGE correlated significantly with urinary albumin/creatinine ratio whereas AOPP correlated with plasma creatinine level.

Conclusions: The connection between plasma levels of both glycooxidation protein products-AGE and AOPP with nephropathy severity, measured by the degree of albuminuria, in T2DM patients was observed. We can suggest that the AOPP better reflect the progression of kidney damage than AGE in examined diabetic patients.
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http://dx.doi.org/10.1002/dmrr.885DOI Listing
October 2008

[Oxidative-antioxidative balance disturbance and risk factors as well as vascular complications in patients with diabetes type 2].

Wiad Lek 2007 ;60(7-8):329-34

Z Katedry i Kliniki Angiologii, Nadciniénia Tetniczego i Diabetologii oraz z Wrocławiu.

Unlabelled: Hyperglycemia in patients with type 2 diabetes induces many pathological states, especially in disturbances cells' metabolism, like disorders of oxidative-antioxidative balance. The advantage of reactive oxygen species (ROS) over antioxidants is a cause of oxidative stress and creates an oxidative molecular damage of proteins, lipids, carbohydrates and nucleotides. It causes tissue degeneration, particularly in vascular system. The aim of our study was to evaluate the oxidative-antioxidative balance in patients with type 2 diabetes on the basis of selected parameters of the oxidative stress protein damage: thiol- (SH), carbonyl- (CO) and amino- (NH2) groups as well as advanced oxidation protein product (AOPP), as AOPP/albumin index as well as concentration of low molecular antioxidants (vitamin C, E, urinary acid, bilirubin). The total radical trapping antioxidant parameter (TRAP) was calculated also according to the mathematics formula. We have examined relationship between this parameters and duration of diabetes and vascular complications as well as risk factors like: hypertension, lipid disorders and obesity.

Material And Methods: Fifty-three patients with type 2 diabetes and 21 healthy persons were examined. The concentrations of SH and CO groups, AOPP as well as vitamin C were assessed colorimetrically, NH2 groups fluorimetrically and vitamin E by high-performance liquid chromatography (HPLC) method. The urinary acid and bilirubin were evaluated using routine clinical assays.

Results: In patients with type 2 diabetes in comparison to healthy persons were affirmed: the significantly higher concentration of CO groups and AOPP as well as significantly lower concentration of SH groups; the lower concentration of vitamin C and TRAP value (statistically significant) and vitamin E (NS); the higher level of urinary acid (statistically significant) and bilirubin (NS).

Conclusions: The measurement of AOPP seems to be the best marker of oxidative stress in patients with type 2 diabetes, because significant increase of AOPP concentration was observed in patients with long-lasting diabetes (more then 10 years) with macroangiopathy, as well as in obese patients and ones with lipid disorders.
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February 2008

[Ischemia modified albumin--specific marker in cardiological diagnostics?].

Wiad Lek 2008 ;61(10-12):263-8

Katedry i Kliniki Angiologii, Nadciśnienia Tetniczego i Diabetologii oraz, Akademii Medycznej we Wrocławiu.

Ischemia modified albumin (IMA) is a new biological marker for early identification of chest pain and ruling out myocardial infarction among patients with acute syndromes submitting to emergency department. Recently IMA has been investigated in the light of other cardiac markers (cTnT, CK-MBmas, NT-proBNP) in various states of ischemia (acute coronary syndromes, after percutaneous coronary intervention, in coronary vasospasm). Ischemia modified albumin levels were elevated in these states what suggests myocardial ischemia. However decrease in IMA concentration after exercise-induced skeletal muscle ischemia still remains unclear. Increased IMA concentration in patients with acute ischemic stroke and exposed to trauma limits its ability for detection myocardial ischemia. Specificity of IMA measurement is limited also in patients with peripheral vascular disease, systemic sclerosis, diabetes, end stage renal disease, pulmonary embolism and other pathological states with accompanying oxidative stress.
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April 2009

[Molecular aspects of aminoglycoside nephrotoxicity].

Postepy Hig Med Dosw (Online) 2007 Sep 28;61:511-8. Epub 2007 Sep 28.

Katedra i Zakład Biochemii Farmaceutycznej Akademii Medycznej we Wrocławiu.

Aminoglycosides are potent bactericidal antibiotics particularly active against aerobic Gram-negative bacteria. This review focuses on the recent concept of a molecular understanding of aminoglycoside-induced nephrotoxicity. As receptor-mediated endocytosis plays an important role in the accumulation of aminoglycosides in renal proximal tubules, the biochemical properties of the two main receptors, megalin and cubilin, involved in this process are described. Literature data on megalin and acidic phospholipids as potential targets for preventing aminoglycoside-induced nephrotoxicity are also presented.
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September 2007

AOPP and its relations with selected markers of oxidative/antioxidative system in type 2 diabetes mellitus.

Diabetes Res Clin Pract 2007 Aug 1;77(2):188-92. Epub 2007 Mar 1.

Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Faculty of Pharmacy, Szewska 38/39, 50-139 Wrocław, Poland.

Background: The aim of this study was to evaluate the selected components of the oxidative/antioxidative system in T2DM; estimation of relationships between them; search for the more expressive one and examine their alterations in angiopathy and obesity.

Methods: In 94 diabetic patients and 36 healthy people, plasma levels of TRAP, as a marker of antioxidative defence, as well as concentrations of CO, SH, and NH(2) groups and AOPP, as markers of oxidative protein damage (OPD) were determined.

Results: Patients had significantly lower levels of TRAP and SH groups, as well as higher NH(2), CO and AOPP in comparison to control. Significant correlation was observed between TRAP and SH groups and AOPP as well as between AOPP and SH and CO groups. Concentration of AOPP was significantly higher in the macroangiopathy and obese subgroups.

Conclusions: Our results support the idea that diabetes mellitus is a complex metabolic disorder with oxidant/antioxidant defence disturbances. Among the studied parameters AOPP showed the most expressive raise in plasma of diabetic patients and significant differences between their subgroups with vascular complications and overweight. We can conclude that AOPP seems to be considered as a useful marker to estimate the degree of OPD in diabetic patients.
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http://dx.doi.org/10.1016/j.diabres.2006.12.007DOI Listing
August 2007

Characterization of chicken cystatin binding to rat renal brush-border membranes.

Comp Biochem Physiol B Biochem Mol Biol 2007 Apr 21;146(4):482-8. Epub 2006 Nov 21.

Department of Pharmaceutical Biochemistry, Wrocław Medical University, Szewska 38/39, 50-139 Wrocław, Poland.

Chicken cystatin, a homologue of human cystatin C, like other low-molecular-weight proteins is metabolized by renal proximal tubule cells. However, the precise mechanism(s) of this process has not been elucidated yet. To characterize chicken cystatin binding to renal brush-border membranes, the incubation of fluorescein labelled protein with rat cortical homogenate was performed. Saturation-dependent and reversible binding with low affinity (K(d)=3.67-4.07 microM) and high capacity (B(max)=2.32-2.79 nmol/mg) was observed. Bovine albumin was the most potent competitor (K(i)=0.7 microM) among other megalin/cubilin ligands tested. The presence of Ca(+2) ions was necessary to effective cystatin binding by brush-border membranes. Obtained data strongly support the hypothesis that chicken cystatin is a novel ligand for megalin/cubilin receptors tandem on proximal tubular cells.
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http://dx.doi.org/10.1016/j.cbpb.2006.11.004DOI Listing
April 2007

Urinary activities of cathepsin B, N-acetyl-beta-D-glucosaminidase, and albuminuria in patients with type 2 diabetes mellitus.

Med Sci Monit 2006 May;12(5):CR210-4

Department of Pharmaceutical Biochemistry of the Wrocław Medical University, Wrocław, Poland.

Background: The proximal kidney tubule contains a large number of lysosomes involved in the breakdown of intracellular as well as reabsorbed proteins. When tubular protein reabsorption is overburdened or when there is tubular cell damage, higher urinary excretion of lysosomal enzymes, e.g. cathepsins and N-acetyl-beta-D-glucosaminidase (NAG), can be found. We compared urinary cathepsin B (CB) activity with NAG in diabetic patients.

Material/methods: Using fluorogenic substrates, urinary and plasma CB and NAG activities in 130 type 2 diabetic patients with varying stages of albuminuria and 42 control subjects were determined. Early morning urine samples were used.

Results: In the patients, only higher values of plasma NAG were found. In urine, CB and NAG activities increased progressively from normoalbuminuria, through microalbuminuria to macroalbuminuria group. The normoalbuminuria group had both enzyme activities higher than healthy controls. Urine CB activity in the patients also increased gradually to tertiles of urinary NAG. Only urinary CB activity was significantly associated with glycemic state. The correlation was stronger in the patients with poor glycemic control. The plasma/urine ratios for both CB and NAG decreased in the patients compared with controls.

Conclusions: Determination of urinary CB activity might be useful as a non-invasive surrogate marker of incipient nephropathy.
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May 2006

Total and lipid-bound plasma sialic acid as diagnostic markers in colorectal cancer patients: correlation with cathepsin B expression in progression to Dukes stage.

J Exp Ther Oncol 2006 ;5(3):223-9

Department of Pathophysiology, Wroclaw Medical University, Marcinkowski 1 Street, Wroclaw, Poland.

Purpose: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease.

Methods: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis.

Results: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed.

Conclusion: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.
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May 2006

Expression of cystatin C in clinical human colorectal cancer tissues.

J Exp Ther Oncol 2005 ;5(1):49-53

Department of Forensic Medicine, Molecular Technical Unit, Wroclaw Medical University, Curie-Sklodowskiej 52, 50-369 Wroclaw, Poland.

We studied the relation between the antipapain activity of cysteine proteinase inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti-chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour tissues immuno-peroxidase reactivity was present in the cytoplasm and on the cell surface membranes. Sections of non malignant tissues showed no staining. The percentages of positive staining were greater for adenocarcinoma than carcinoma,100% and 77% respectively. Antipapain activity which was increased in malignant tissues in comparison to control, rose successively from well differentiated carcinomas through moderately to poor differentiated. Invasive adenocarcinomas had higher antipapain activity than noninvasive ones. The results indicated that immunohistochemical detection of cystatin using anti-chicken cystatin antibodies could be useful in studying the prognostic significance of cystatin C expression in colorectal cancer.
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March 2006

[Stefin A--potential application in oncological laboratory diagnosis].

Authors:
Maria Warwas

Pol Merkur Lekarski 2005 Jul;19(109):86-9

Katedra i Zakład Biochemii Farmaceutycznej Akademii Medycznej we Wrocławiu.

This is a review of studies on stefin A, an intracellular cysteine peptidase inhibitor of cystatin superfamily. Cystatins and target cysteine peptidases, such as cathepsins B and L have been implicated in malignant progression. The biochemical characteristics of human stefin A and its functions are presented. Special attention was paid to the potential usefulness of stefin A determination in serum and tissue cytosol (ELISA test) or tissue sections (immunohistochemistry) in the oncological laboratory diagnosis.
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July 2005

[Serum stefin A in patients with type 2 diabetes].

Pol Arch Med Wewn 2004 Mar;111(3):319-25

Katedra i Zakład Biochemii Farmaceutycznej we Wrocławiu.

Stefin A is the low-molecular, intracellular inhibitor of the human lysosomal cysteine proteinases, cathepsins B, H and L. The concentration of this inhibitor in plasma and in other biological fluids shows not only local expression and secretion but also immunity of the whole organism. The aim of our study was to examine if concentration of stefin A in plasma of patients with diabetes type 2 is different than in healthy subjects, depends on vascular complications, body mass index, glycaemic control and whether exists the relationship between activities of cathepsin B (CB) as well as N-acetyl-beta-D-glucosaminidase (NAG). In plasma of 62 diabetic patients and 14 control subjects, concentration of stefin A (using ELISA test) and activities of CB and NAG (using fluorescence methods) were investigated. Concentration of stefin A (4.95 micrograms/l) in comparison to control (2.80 micrograms/l) increased statistically significantly (p < 0.05). The highest increase of stefin A was discovered in patients with macrovascular complication (7.70 micrograms/l) and was significantly different (p < 0.01) in comparison with control group and patients with microangiopathy as well as both types of complications (micro- and macroangiopathy). Significantly higher concentration of stefin A was noted in patients with overweight and obesity (5.50 micrograms/l and 6.05 micrograms/l). No influence of glycaemic short and long term control on concentration of this inhibitor was observed. In patients divided into subgroups according to increasing plasma NAG activity, increase of stefin A was noted successively from subgroup K2 to K4 (NAG from 8.80 U/l to above 12.82 U/l). The results indicate contribution of stefin A in pathogenesis of vascular complications in patients with diabetes type 2 and its relationship with obesity.
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March 2004

[Cathepsin B and pro-drug activation].

Authors:
Maria Warwas

Postepy Hig Med Dosw 2003 ;57(6):701-12

Katedra i Zakład Biochemii Farmaceutycznej Akademii Medycznej we Wrocławiu.

Cathepsin B (CB) is a tumour-associated cysteine peptidase, which plays an important role in the proteolytic cascade involved in cancer invasion. Therefore, pro-drugs specifically activated by CB are expected to possess enhanced tumour selected properties. This paper presents the actual stage of knowledge on anticancer therapy strategies using CB as a side-specific activator of immuno- or polymer-conjugates (Antibody Directed Enzyme Pro-Drug Therapy or Polymer Directed Enzyme Pro-Drug Therapy, respectively). Usefulness of CB determinations in the laboratory diagnosis of neoplastic diseases is also presented.
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May 2004

[Cathepsin B activity and concentration of elastase and alpha-1 proteinase inhibitor complex in non-small-cell lung cancer: 2 year follow-up study].

Pol Merkur Lekarski 2003 May;14(83):417-20

Katedra i Klinika Chorób Płuc Akademii Medycznej we Wrocławiu.

In 21 patients with non-small-cell lung cancer subjected to radical surgery followed by 3 cycles of chemotherapy, serum cathepsin B activity and plasma E-alpha 1IP concentration in peripheral blood and tumour arterial and venous blood were studied. Cathepsin B activity was determined by a fluorometric assay. E-alpha 1IP concentration was measured with an ELISA kit. The measurements were performed before surgery, before each chemotherapy cycle and every 60 days after chemotherapy completion, for 2 years. All the patients (n = 21) were divided into 2 subgroups: without metastases n = 16 and with metastases n = 5. There was no significant difference between preoperative serum cathepsin B activity and E-alpha 1IP plasma values in peripheral blood and blood coming from tumour artery and vein. The surgery and chemotherapy caused a statistically significant decrease of serum cathepsin B activity and plasma E-alpha 1IP concentration both in the whole group and in the subgroup without metastases. A significant increase of cathepsin B activity in comparison to initial values was observed 2,5-4 months before cerebral metastasis appeared in the subgroup with metastases. The elevation of E-alpha 1IP concentration preceded the increase of cathepsin B activity in this subgroup. It was not statistically significant. A decrease of cathepsin B and E-alpha 1IP values was observed after cerebral metastasis excision.
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May 2003
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