Prevention of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

Serum ß-glucuronidase as a potential colon cancer marker: a preliminary study.

AIM: Colorectal cancer is characterized by high morbidity and mortality in developed countries. The lack of low-cost, easy-to-use screening diagnostic methods is one of the causes of late diagnosis of colorectal cancer. Beta-glucuronidase (GLU) is a lysosomal exoglycosidase involved in degradation of glycosaminoglycans of the cell membranes and extracellular matrix of normal and cancerous colon tissues. The aim of our research was to evaluate the activity of GLU in the serum of colorectal cancer and estimate its potential value in the diagnosis of colorectal cancer. MATERIAL AND METHODS: Blood samples were collected from 21 patients with colorectal adenocarcinoma and 17 healthy subjects. GLU activity was determined by the colorimetric method of Marciniak et al. by measuring the amount of p-nitrophenol released from 4-nitrophenyl-beta-D-glucuronide, at λ = 405 nm. RESULTS: We found significantly greater activity of GLU (p<0.0001) in the serum of patients with colorectal cancer, as compared to the healthy subjects. The serum GLU activity significantly differentiates patients with colorectal cancer from healthy individuals. CONCLUSIONS: Serum GLU activity has diagnostic value and may be used in the diagnosis of colon adenocarcinoma.

Salivary exoglycosidases as markers of alcohol dependence.

BACKGROUND: Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, ß-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. AIM: To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), ß-galactosidase (GAL), and ß-glucuronidase (GLU), and their applicability as markers of alcohol dependence. METHODS: The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. RESULTS: We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. CONCLUSIONS: Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence).

Glycosylation changes in the salivary glycoproteins of alcohol-dependent patients: a pilot study.

AIM: Glycosylation of serum proteins is affected with prolonged heavy drinking, and carbohydrate deficient transferrin (CDT) is well established and highly specific biomarker of sustained alcohol consumption. However, total amount of sialic acid is not the only glycoepitope that may be altered as a result of the disease. This work is focused on glycan structures altered in salivary glycoproteins of alcoholics, indicating the most efficient carriers of such marker glycoepitopes. METHODS: Salivary glycoproteins of 31 alcohol-dependent patients and 21 healthy controls were studied by means of lectin ELISA and lectin blotting with the lectins specific for core and antennary fucose, α2,3-bound sialic acid as well as T and Tn antigens in O-glycans. RESULTS: In direct lectin ELISA, core fucosylation, α2,3 sialylation and expression of T-antigen were significantly lowered in the saliva of alcohol-dependent patients. In lectin blotting ten glycoprotein bands were analyzed. The profile of disease-related alterations was found to be complex, but all six lectins studied here were able to detect altered glycan structures. In some glycoproteins the tendency to correct the glycosylation profile was observed after 7 weeks of abstinence. CONCLUSION: Alterations in the glycosylation profiles in the salivary glycoproteins of alcohol-dependent people were found. Some of salivary glycoproteins, such as α-amylase, clusterin, haptoglobin, heavy and light chains of immunoglobulins, and transferrin, seem to be worthy of detailed glycosylation analysis in the detection of alcohol dependence. Further studies may allow one to estimate if such glycomarkers may also reflect the amount of alcohol intake or the duration of alcohol intake.

The role of carnitine in the perinatal period.

Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small hydrophilic molecule derived from protein-bound lysine, not degraded in the body but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism of long-chain fatty acids (FAs), by transporting them to mitochondria for oxidation, and the intracellular decomposition of branched-chain ketoacids. It also helps to excrete toxic exogenous and nontoxic endogenous organic acids via urine. It further participates in the production of pulmonary surfactant, inhibits free radicals production and demonstrates other antioxidant properties. After delivery, infants dramatically increase energy demands for movement, growth, differentiation and maintenance of the body temperature that strongly depend on FAs oxidation which is facilitated by carnitine. At early stages of life, carnitine biosynthesis is less efficient than in adults and immature infants have less carnitine tissue reserves than term infants. Carnitine supplementation is recommended in newborns with aciduria, childhood epilepsy associated with valproate-induced hepatotoxicity, in kidney-associated syndromes, and premature infants receiving total parenteral nutrition. Concentrations of carnitine and acylcarnitines in neonatal blood have been postulated a useful tool for the diagnosis of type 1 diabetes, as well as the detection and monitoring of many inherited and acquired metabolic disorders. Taking into account the complex metabolic role of cellular FAs transporters, further studies are needed on indications and contraindications for carnitine supplementation in different clinical settings during early developmental period.

The diagnostics of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent human malignant neoplasms. CRC has an estimated incidence of more than 1,000,000 new cases annually worldwide. Approximately one out of three people who develop CRC dies from the disease. Furthermore, CRC often affects inhabitants of industrialized countries in comparison to less developed countries. Several markers of colon cancer, including CEA, CA-19-9, TPS, TAG-72 and lysosomal hydrolases, have been identified and are now being adopted in routine clinical practice. Increased values of these markers are often the first signal of recurrence or metastases, which is useful in prediction and prognosis of clinical outcome of patients with CRC. Determination of the activity of lysosomal exoglycosidases in body fluids may bring some hope of improving diagnosis of colorectal cancer. However, it has to be remembered that currently the most effective diagnostic method of CRC is endoscopy.

Binge drinking-induced subtle myocardial injury.

BACKGROUND: Most of the clinical, histopathological, and biochemical studies consider the effect of chronic alcohol intoxication on myocardial injury. Much less attention has been paid to acute alcohol (binge drinking)-induced cardiotoxicity, even though alcohol binging is much more common than alcohol dependence. METHODS: We briefly present some of the binge drinking-induced "holiday heart" effects. The literature was searched to find effects of alcohol on heart. RESULTS: In binge drinking, the literature has demonstrated transient myocardial subtle changes in cardiac magnetic resonance, increased serological markers of myocardial injury and inflammation, abnormal cardiac rhythm, changes in other biochemical and ultrastructural indices of myocardial dysfunction, as well as changes in metabolism, blood pressure, heart rate, thrombosis/fibrinolysis processes, and coronary vasoconstriction. CONCLUSIONS: Although acute low alcohol exposure has widely proven positive effect on myocardial function, heavy acute drinking frequent events are related to adverse cardiovascular effects.

Salivary innate defense system in type 1 diabetes mellitus in children with mixed and permanent dentition.

OBJECTIVE: It should be expected that type 1 diabetes mellitus may disturb innate and acquired immunity. There are no data on type 1 diabetes mellitus-related changes in the salivary flow and the protein output responsible for the innate immunity of saliva depending on the quality of dentition reflecting the age of child. The aim of this work was the evaluation of parameters responsible for the innate immunity of saliva in children and adolescents with type 1 diabetes mellitus. MATERIALS AND METHODS: In diabetic children, adolescent and healthy volunteers, the salivary flow, the output and the concentration of the activity of peroxidase (colorimetry), lysozyme (radial immunodiffusion) and lactoferrin (ELISA) were determined. RESULTS: In children with mixed and permanent dentition, type 1 diabetes mellitus significantly decreases (as compared with the appropriate controls) the unstimulated salivary flow, the output, concentration of peroxidase and the output of the lysozyme and lactoferrin. CONCLUSION: In conclusion, it may be stated that type 1 diabetes mellitus causes functional changes in the salivary glands, resulting in a decrease of the salivary flow and weakening of the salivary innate defense system, thus creating a threat to the oral and general health of type 1 diabetes mellitus children. The results showed that the salivary glands of younger children, when compared to adolescents with type 1 diabetes mellitus, are more susceptible to the injurious effects of the disease.

Salivary exoglycosidases in the detection of early onset of salivary gland involvement in rheumatoid arthritis.

INTRODUCTION: The aim of the present study was to evaluate the possibility of making use of the specific activity of N-acetyl-ß-hexosaminidase, its isoenzymes and ß-glucuronidase--potential indicators of salivary gland damage--in the detection of early onset of salivary gland impairment in RA, which is also demonstrated by xerostomia. MATERIAL/METHODS: For this purpose RA xerostomic salivary patients (unstimulated salivary flow >0.1 mL/min) were compared with RA xerostomic hyposalivary patients (unstimulated salivary flow ≤0.1 mL/min), RA patients without xerostomia (unstimulated salivary flow >0.1 mL/min) and generally healthy controls (unstimulated salivary flow >0.1 mL/min, without xerostomia). Salivary N-acetyl-ß-hexosaminidase, its isoenzymes A and B, and ß-glucuronidase specific activity were determined according to the Marciniak et al. method. The protein content in the unstimulated saliva was determined by the bicinchoninic acid method. RESULTS: In xerostomic rheumatoid arthritis patients, the specific activity of salivary ß-glucuronidase and isoenzyme A was significantly higher than in the healthy controls but the specific activity of salivary N-acetyl-ß-hexosaminidase, its isoenzyme B and ß-glucuronidase was significantly lower than in xerostomic hyposalivary rheumatoid arthritis patients. CONCLUSIONS: We suggest a simple, safe and cheap method for the determination of exoglycosidases as a useful tool for the diagnosis of early stages of salivary gland involvement in rheumatoid arthritis.

Plasma carnitine concentrations after chronic alcohol intoxication.

BACKGROUND: Carnitine transports fatty acids from the cytoplasm to the mitochondrial matrix, where the fatty acids are oxidized. Chronic alcohol consumption reduces the concentration of carnitine and interferes with oxidative processes occurring in the cell. AIM: The assessment of carnitine concentrations in plasma of chronically intoxicated alcohol dependent persons in a 49-day abstinence period. MATERIAL/METHODS: The study included 31 patients (5 women and 27 men) aged from 26 to 60 years (44.6 ± 8.9) and 32 healthy subjects (15 women and 17 men) aged 22-60 years (39.8 ± 9.4). The patients' alcohol dependence ranged from 2 to 30 years (13.6 ± 7.5). Examined subjects consumed 75-700 g of ethanol/day (226.9 ± 151.5). Plasma concentrations of free and total carnitine were measured three times: at the first (T0), 30th (T30) and 49th (T49) day of hospital detoxification. Free (FC) and total (TC) carnitine were determined by the spectrophotometric method. Plasma acylcarnitine (AC) concentration was calculated from the difference between TC and FC; then the AC/FC ratio was calculated. To determine statistically significant differences for related variables, Student's t-test was used. RESULTS: At T0, alcoholics had significantly lower concentration of FC and TC (p < 0.05) in plasma, as compared to the control group. In comparison to controls, at T30, plasma TC and FC (p < 0.01) as well as AC (p < 0.001) were reduced. The lowest concentration of TC, FC and AC (p < 0.001)was found at T49. The ratio of AC/FC at T0 had a tendency to be higher in alcoholics than in the control group (p = 0.05), whereas at T49 it was significantly lower in alcoholics as compared to the control subjects (p < 0.05). CONCLUSIONS: Chronic alcohol intoxication causes a plasma deficiency of carnitine. Forty-nine days of abstinence showed a significant decrease in the concentration of TC, FC and AC. Further research is necessary to clarify whether a low level of plasma carnitine after chronic alcohol intoxication is caused by the uptake of blood carnitine by tissues such as liver or muscles. In alcoholics the supplementation of carnitine is recommended in the case of a low level of plasma carnitine.

Activity of N-acetyl-ß-D-hexosaminidase in the saliva of children with type 1 diabetes.

BACKGROUND/AIM: Type 1 diabetes is one of the most common chronic diseases in children. The aim of the study was to evaluate the catabolism of glycoconjugates in saliva of children with type 1 diabetes, by measurement of the activity of N-acetyl-ß-D-hexosaminidase (HEX) in their saliva. MATERIAL/METHODS: The study was performed in 65 children with type 1 diabetes and 39 healthy children. Salivary HEX activity was determined spectrophotometrically by the method of Zwierz et al. in the modification of Marciniak et al. Protein was determined by the bicinchoninic acid method (BCATM Assay Protein Kit). Concentration of the HEX activity was expressed in pKat/mL and HEX specific activity in pKat/µg of protein. RESULTS: A significant increase in the concentration and the specific activity of HEX in the saliva of children with type 1 diabetes, compared to healthy children, was found. CONCLUSIONS: Type 1 diabetes increases salivary catabolism of glycoconjugates reflected by the significant increase in the activity of HEX in the saliva of children with type 1 diabetes compared to healthy children. The salivary HEX activity may be used in the diagnosis of children with type 1 diabetes after confirmation of our results on a larger cohort of children with type 1 diabetes.

The activity of serum beta-galactosidase in colon cancer patients with a history of alcohol and nicotine dependence: preliminary data.

INTRODUCTION: Beta-galactosidase (GAL) is a lysosomal exoglycosidase involved in the catabolism of glycoconjugates through the sequential release of beta-linked terminal galactosyl residues. The stimulation of activity of exoglycosidases and other degradative enzymes has been noted in cancers as well as in alcohol and nicotine addiction separately. This is the first study to evaluate the activity of the serum senescence marker GAL in colon cancer patients with a history of alcohol and nicotine dependence, as a potential factor of worse cancer prognosis. MATERIAL AND METHODS: The material was serum of 18 colon cancer patients and 10 healthy volunteers. Ten colon cancer patients met alcohol and nicotine dependence criteria. The activity of beta-galactosidase (pkat/ml) was determined by the colorimetric method. Comparisons between groups were made using the Kruskal-Wallis analysis and differences evaluated using the Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the statistical dependence between two variables. RESULTS: The activity of serum GAL was significantly higher in colon cancer patients with a history of alcohol and nicotine dependence, in comparison to colon cancer patients without a history of drinking/smoking (p=0.015; 46% increase), and the controls (p=0.0002; 81% increase). The activity of serum GAL in colon cancer patients without a history of alcohol/nicotine dependence was higher than the activity in the controls (p = 0.043; 24% increase). DISCUSSION/CONCLUSION: Higher activity of beta-galactosidase may potentially reflect the accelerated growth of the cancer, invasion, metastases, and maturation, when alcohol and nicotine dependence coincide with colon cancer. For a better prognosis of colon cancer, alcohol and nicotine withdrawal seems to be required.

[Isoforms A and B of lysosomal N-acetyl-beta-D-hexosaminidase in serum and urine of parenterally fed patients]. / Izoenzymy A i B lizosomalnej N-acetylo-beta-D-heksozoaminidazy w surowicy i moczu chorych zywionych pozajelitowo.

UNLABELLED: Parenteral nutrition entails numerous metabolic complications resulting from food bypass of the gastrointestinal tract. Up to now have not been established all complications of parenteral nutrition, despite intensive research and clinical observations. Knowledge of the biochemical changes resulting from parenteral nutrition is essential to effective prevention, early detection and effective treatment of the metabolic disorders induced by parenteral nutrition. The aim of the study was to evaluate the catabolism of glycoconjugates of parenterally fed patients, reflected by the activity of N-acetyl-beta-D-hexosaminidase (HEX): HEX A and HEX B isoenzymes in serum and urine. MATERIAL AND METHODS: Samples of blood and urine were collected from 23 patients: before intravenous alimentation, at start, as well as of fifth and tenth day of parenteral nutrition. The activity of HEX A and HEX B in serum and urine was determined by the colorimetric method of Zwierz et al. as modified by Marciniak et al. The activity of urinary HEXA and HEX B has been calculated per 1 mg of creatinine. RESULTS: The activity of serum HEXA significantly decreased at fifth day, in comparison to the activity before parenteral alimentation, and significantly increased at tenth day of parenteral nutrition. The activity of HEX B in serum increased significantly at fifth and tenth day of the parenteral nutrition. CONCLUSIONS: Parenteral nutrition alter the catabolism of glycoconjugates, reflected by significant changes in serum HEX A and HEX B activities. Urine was the not appropriate material to evaluate the catabolism of glycoconjugates in view of HEX A and HEX B activities.

Activity of alpha-fucosidase and beta-glucuronidase in serum and urine of patients administered parenteral nutrition.

BACKGROUND: In hospital patients suffering from adverse clinical and biochemical symptoms of malnutrition, it is often necessary to employ parenteral nutrition to avoid the body's tissue becoming broken down by being metabolised. Thus, the patient's welfare and survival can be supported throughout any periods of medical crisis. Two of the enzymes responsible for metabolising glycoconjugates are alpha-fucosidase (FUC) and beta-glucuronidase (GLU), present in lysosomes. They release fucose or glucuronic acid from the non-reducing end of oligosaccharide chains. OBJECTIVE: To determine the effect of parenteral nutrition administered to ill patients, on glycoconjugate metabolism, by measuring serum and urinary activities of FUC and GLU. Material and methods. Blood samples and the daily urine collection were taken from 23 patients' who had been undergoing parenteral nutrition for either 5 or 10 days, as well as from a baseline sample. Enzyme activities in serum and urine were determined by the method of Zwierz et al. RESULTS: Serum FUC activities were significantly lower after 10 days compared to 5, (p< 0.0172), whereas GLU activities were significantly lower after both 5 and 10 days, (p< 0.0007 and p< 0.0208 respectively), compared to levels before starting parenteral nutrition. GLU activities were however higher after 10 days than those after 5 days, (p< 0.0023). In urine, FUC activities were significantly decreased after 10 days compared to 5 days after starting parenteral nutrition, (p< 0.0245). Urine GLU activities were unaffected by parenteral nutrition nor was any effect seen on FUC or GLU activities when calculated per 1mg creatinine. CONCLUSIONS: Serum FUC and GLU activities can be used for assessing the effect of parenteral nutrition on glycoconjugate metabolism. The significant decreases of serum GLU activity observed after 5 and 10 days, may serve to indicate that the components of parental nutrition are appropriate and that the body has become suitably adapted to this form of nutrition.

The Effect of Neoglandin on the Activity of N-Acetyl-ß-D-Hexosaminidase in the Serum and Urine of Alcohol-Dependent Men.

Dietary supplementation of gamma-linolenic acid (GLA) in the form of a commercial drug neoglandin (containing GLA and vitamin E), in people following alcohol abuse allows bypassing of the ineffective delta-6-desaturase system involved in the transformation of linoleic acid into GLA. Determination of the activity of N-acetyl-ß-D-hexosaminidase (HEX) in the serum and urine reflects neoglandin action on the catabolism of glycoconjugates and the functioning of liver and kidneys in people following alcohol abuse. MATERIAL AND METHODS: The serum and urine were collected from men with alcohol dependence, treated (n = 31, age 33.16 ± 9.72 years) and not treated (n = 50, age 35.46 ± 11.37 years) with neoglandin. HEX activity were assayed in the supernatants by the colorimetric method, with the p-nitrophenyl derivative of sugar as substrate. RESULTS: Our study on alcoholic men not treated with neoglandin indicates a significantly higher concentration of the serum and urinary HEX activity (nKat/L) on day 1 compared to days 7, 10, 14 and 30 (p < 0.001). For days 14 and 30 (p < 0.01), the urinary HEX activity was expressed in µKat/kgCr. No significant differences were observed in the activity of serum (nKat/L) and urinary (nKat/L and µKat/kgCr) HEX in alcoholics during treatment with neoglandin compared to day 1 of neoglandin treatment. We found significantly different (p < 0.05) concentration of HEX activity (nKat/L) in serum of alcohol-dependent men treated with neoglandin compared to those not taking neoglandin on days 7, 10, 14 and 30 of treatment. The urinary concentration of HEX activity (nKat/L) on days 1, 4, 10 and 30 and HEX activity in µKat/kgCr on days 1, 4 and 7 it was significantly higher (p < 0.05) during the treatment of alcohol-dependence without the use of neoglandin as compared to alcoholics treated with neoglandin. We found a positive correlation between the amount of alcohol consumed and the urinary activity of HEX in the early phase after alcohol withdrawal and a lack of correlation between the HEX activity in serum and urine of alcohol-dependent men not treated with neoglandin. CONCLUSIONS: Neoglandin supplementation in alcoholic men significantly slows down the catabolism of glycoconjugates, thus reducing the effects of ethanol poisoning that are harmful to the kidneys. Neoglandin reduces the harmful effects of ethanol poisoning more on the kidneys than on the liver. The activity of HEX in the serum may be used in monitoring the treatment of alcoholism and whether alcohol reuse occurred during the therapy. In the early stages of alcohol withdrawal, urinary HEX activity can be used as a marker of the amount of alcohol consumed during previous alcohol abuse.

Sibutramine-induced mania as the first manifestation of bipolar disorder.

BACKGROUND: Sibutramine, used in obesity treatment, has been associated with many neuropsychiatric side effects including hypomanic and manic episodes. Hypomanic/manic episodes related to sibutramine treatment were earlier reported in patients who had previous history of bipolar disorder, after sibutramine overdose, after over-the-counter product illegally containing very high dose of sibutramine, together with psychotic symptoms, in organic patient, or after interaction of sibutramine with other drugs. CASE PRESENTATION: We report the first case of a patient with clear manic episode, after treatment with recommended dose of sibutramine, without previous history of mood disorders, organic changes or drug interactions, that was followed by episode of depression. CONCLUSION: Minimal recommended dose of sibutramine induced manic episode that was the first manifestation of bipolar disorder. The manic episode, associated with sibutramine treatment, was induced in a person without previous history of mood disorders. Potential risks associated with the treatment of obesity using sibutramine warn physicians to be alert not only to common and cardiovascular but also to psychiatric adverse effects. A careful assessment of patient's mental state and detailed psychiatric family history should be done before sibutramine treatment. In patients with a family history for bipolar disorder the use of even minimal dose of sibutramine should be contraindicated.

Glycoconjugate markers of joint diseases.

A number of different types of glycoconjugate are found associated with joint tissue and fluids, comprising glycoproteins, glycolipids and glycosaminoglycans. Oligosaccharide chains of glycoconjugates are degraded by exoglycosidases, and the dominant exoglycosidase found in human blood, synovial fluid, the synovial membrane and chondrocytes of articular cartilage is HEX (N-acetyl-ß-hexosaminidase). HEX is localized mostly intracellularly in synovial cells. Serum activity of HEX may be used to monitor the course and efficiency of treatment of Lyme arthritis, and activity of HEX, above 10 µkat/kg of protein in the synovial fluid, suggests rheumatoid disease. There is a shortage of HEX inhibitors able to penetrate synoviocytes, so the development of drugs which inhibit synthesis and/or the activity of HEX will be a promising field for future investigations.

Carbohydrate markers of pancreatic cancer.

Pancreatic cancer is the fourth most common cause of death from cancer in the world and the sixth in Europe. Pancreatic cancer is more frequent in males than females. Worldwide, following diagnosis of pancreatic cancer, <2% of patients survive for 5 years, 8% survive for 2 years and <50% survive for only approx. 3 months. The biggest risk factor in pancreatic cancer is age, with a peak of morbidity at 65 years. Difficulty in the diagnosis of pancreatic cancer causes a delay in its detection. It is one of the most difficult cancers to diagnose and therefore to treat successfully. Additional detection of carbohydrate markers may offer a better diagnosis of pancreatic cancer. Carbohydrate markers of cancer may be produced by the cancer itself or by the body in response to cancer, whose presence in body fluids suggests the presence and growth of the cancer. The most widely used, and best-recognized, carbohydrate marker of pancreatic cancer is CA 19-9 [CA (carbohydrate antigen) 19-9]. However, the relatively non-specific nature of CA 19-9 limits its routine use in the early diagnosis of pancreatic cancer, but it may be useful in monitoring treatment of pancreatic cancer (e.g. the effectiveness of chemotherapy), as a complement to other diagnostic methods. Some other carbohydrate markers of pancreatic cancer may be considered, such as CEA (carcinoembryonic antigen), CA 50 and CA 242, and the mucins MUC1, MUC2 and MUC5AC, but enzymes involved in the processing of glycoconjugates could also be involved. Our preliminary research shows that the activity of lysosomal exoglycosidases, including HEX (N-acetyl-ß-D-hexosaminidase), GAL (ß-D-galactosidase), FUC (α-L-fucosidase) and MAN (α-D-mannosidase), in serum and urine may be used in the diagnosis of pancreatic cancer.

Glycoconjugates in the detection of alcohol abuse.

Up to 30% of all hospital admissions and health-care costs may be attributable to alcohol abuse. Ethanol, its oxidative metabolites, acetaldehyde and ROS (reactive oxygen species), non-oxidative metabolites of alcohol [e.g. FAEEs (fatty acid ethyl esters)] and the ethanol-water competition mechanism are all involved in the deregulation of glycoconjugate (glycoprotein, glycolipid and proteoglycan) metabolic processes including biosynthesis, modification, transport, secretion, elimination and catabolism. An increasing number of new alcohol biomarkers that are the result of alcohol-induced glycoconjugate metabolic errors have appeared in the literature. Glycoconjugate-related alcohol markers are involved in, or are a product of, altered glycoconjugate metabolism, e.g. CDT (carbohydrate-deficient transferrin), SA (sialic acid), plasma SIJ (SA index of apolipoprotein J), CETP (cholesteryl ester transfer protein), ß-HEX (ß-hexosaminidase), dolichol, EtG (ethyl glucuronide) etc. Laboratory tests based on changes in glycoconjugate metabolism are useful in settings where the co-operativeness of the patient is impaired (e.g. driving while intoxicated) or when a history of alcohol use is not available (e.g. after trauma). In clinical practice, glycoconjugate markers of alcohol use/abuse let us distinguish alcoholic from non-alcoholic tissue damage, having important implications for the treatment and management of diseases.

Exoglycosidase markers of diseases.

Exoglycosidases are hydrolases involved in lysosomal degradation of oligosaccharide chains of glycoconjugates (glycoproteins, glycolipids and proteoglycans). In tissues and body fluids, a higher exoglycosidase specific activity is found in N-acetyl-ß-hexosaminidase, than ß-glucuronidase, α-L-fucosidase, ß-galactosidase, α-mannosidase and α-glucosidase. Determination of exoglycosidases (especially N-acetyl-ß-hexosaminidase and ß-glucuronidase) in body fluids could be an inexpensive, easy to perform and sensitive test for pathological evaluation, as well as in screening and monitoring many diseases, including alcohol abuse, risk of arteriosclerosis, bacterial infections (e.g. Lyme borreliosis), chronic inflammatory processes, such as rheumatoid arthritis and juvenile idiopathic arthritis, asthma, autoimmune hepatitis and primary biliary cirrhosis, as well as cancers.