Jerzy Robert Ładny

Alcohol abuse and glycoconjugate metabolism

The relationship between alcohol consumption and glycoconjugate metabolism is complex and multidimensional. This review summarizes the advances in basic and clinical research on the molecular and cellular events involved in the metabolic effects of alcohol on glycoconjugates (glycoproteins, glycolipids, and proteoglycans). We summarize the action of ethanol, acetaldehyde, reactive oxygen species (ROS), nonoxidative metabolite of alcohol — fatty acid ethyl esters (FAEEs), and the ethanol-water competition mechanism, on glycoconjugate biosynthesis, modification, transport and secretion, as well as on elimination and catabolism processes. As the majority of changes in the cellular metabolism of glycoconjugates are generally ascribed to alterations in synthesis, transport, glycosylation and secretion, the degradation and elimination processes, of which the former occurs also in extracellular matrix, seem to be underappreciated. The pathomechanisms are additionally complicated by the fact that the effect of alcohol intoxication on the glycoconjugate metabolism depends not only on the duration of ethanol exposure, but also demonstrates dose- and regional-sensitivity. Further research is needed to bridge the gap in transdisciplinary research and enhance our understanding of alcohol- and glycoconjugate-related diseases.

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.

Impact of morbid obesity and bariatric surgery on antioxidant/oxidant balance of the unstimulated and stimulated human saliva.

OBJECTIVE There is no study evaluating the influence of morbid obesity and bariatric surgery on antioxidant/oxidant homeostasis of the unstimulated and stimulated human saliva. MATERIALS AND METHODS Salivary flow rate, total antioxidant status (TAS), total oxidant status (TOS), oxidative status index (OSI), the total amount of uric acid (UA), polyphenols (pPh), catalase (CAT), superoxide dismutase 2 (SOD2), specific activity of peroxidase (Px), as well as malondialdehyde (MDA), and advanced glycation end products (AGE) concentrations were determined in the unstimulated (UWS) and stimulated (SWS) whole saliva of patients with morbid obesity before and after bariatric surgery. RESULTS In both UWS and SWS, the total amount of TOS, OSI, SOD2, and MDA was statistically higher in patients with morbid obesity as compared to the healthy controls, as well as significantly lower in the patients treated surgically as compared to the obese patients. The median values of the total amount of TAS, CAT, UA, pPh, and specific activity of Px were significantly reduced in UWS and SWS in patients with morbid obesity as compared to the control group and also statistically elevated in patients after bariatric surgery as compared to the patients with morbid obesity. CONCLUSIONS In morbid obesity, reduced unstimulated and stimulated salivary flow can be observed. Bariatric surgery restored only unstimulated salivary flow to normal values. Disturbances in oxidant/antioxidant homeostasis may be observed in UWS and SWS of obese patients before and after treatment.

Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients

Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann-Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or higher catabolism) or to decreased function of neutrophils affected by the ethanol. The poorer periodontal state in alcohol dependent persons compared to controls may be a result of lower salivary flow and decreased protection of the oral cavity by lactoferrin.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands.

Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

The effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase

Peroxidase is the most important antioxidant enzyme in saliva. Through peroxidation of thiocyanate in the presence of H2O2, peroxidase catalyses the formation of bacteriocidic compounds such as hypothiocyanate. The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase (OPO). A total of 37 volunteers participated in the study. This cohort consisted of 17 male alcohol-dependent smoking patients after chronic alcohol intoxication (AS group, alcohol + smoking) (mean age: 42 years; range: 26–55) (100–700 g/day of alcohol; 10–20 cigarettes/day) and 20 control male social drinkers (CNS group, control non-smokers) with no history of alcohol abuse or smoking (mean age: 42 years; range: 30–53). Salivary peroxidase activity was measured by the colorimetric method. The differences between groups were evaluated using the Mann–Whitney U test. There was significantly higher activity of OPO (p = 0.00001) and significantly lower salivary flow (SF) (p = 0.007) in alcohol-dependent smokers after chronic alcohol intoxication compared to the control group. OPO activity significantly correlated with the number of days of alcohol intoxication, but not with smoking. Gingival index (GI) was significantly higher in smoking alcohol-dependent persons than in the control group, and correlated with OPO activity. The sensitivity of the OPO test was 70% in smoking alcoholics, while specificity was 95%. The increased activity of OPO suggests chronic oxidative stress is more likely due to ethanol action than to smoking. Smoking alcohol-dependent persons have a worse periodontal status than controls. OPO activity as a marker of chronic alcohol abuse may help in the diagnosis of alcoholism.

The Redox Balance in Erythrocytes, Plasma, and Periosteum of Patients with Titanium Fixation of the Jaw

Titanium miniplates and screws are commonly used for fixation of jaw fractured or osteotomies. Despite the opinion of their biocompatibility, in clinical practice symptoms of chronic inflammation around the fixation develop in some patients, even many years after the application of miniplates and screws. The cause of these complications is still an unanswered question. Taking into account that oxidative stress is one of the toxic action of titanium, we have evaluated the antioxidant barrier as well as oxidative stress in the erythrocytes, plasma and periosteum covering the titanium fixation of the jaw. The study group was composed of 32 patients aged 20–30 with inserted miniplates and screws. The antioxidant defense: catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase-1 (SOD1), uric acid (UA), total antioxidant capacity (TAC), as well as oxidative damage products: advanced oxidation protein products (AOPP), advanced glycation end products (AGE), dityrosine, kynurenine, N-formylkynurenine, tryptophan, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total oxidant status (TOS), and oxidative status index (OSI) were evaluated. SOD1 activity (↓37%), and tryptophan levels (↓34%) showed a significant decrease while AOPP (↑25%), TOS (↑80%) and OSI (↑101%) were significantly elevated in maxillary periosteum of patients who underwent bimaxillary osteotomies as compared to the control group. SOD-1 (↓55%), TAC (↓58.6%), AGE (↓60%) and N-formylkynurenine (↓34%) was statistically reduced while AOPP (↑38%), MDA (↑29%), 4-HNE (↑114%), TOS (↑99%), and OSI (↑381%) were significantly higher in the mandibular periosteum covering miniplates/screw compared with the control tissues. There were no correlations between antioxidants and oxidative stress markers in the periosteum of all patients and the blood. As exposure to the Ti6Al4V titanium alloy leads to disturbances of redox balance in the periosteum surrounding titanium implants of the maxilla and the mandible so antioxidant supplementation should be recommended to the patients undergoing treatment of dentofacial deformities with the use of titanium implants. The results we obtained may also indicate a need to improve the quality of titanium jaw fixations through increase of TiO2 passivation layer thickness or to develop new, the most highly biodegradable materials for their production.

Sibutramine-induced mania as the first manifestation of bipolar disorder

BackgroundSibutramine, 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 presentationWe 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.ConclusionMinimal 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.

The Salivary β-HEX A% Index as an Excellent Marker of Periodontitis in Smoking Alcohol-Dependent Persons

Background. Severe periodontitis leading to tooth loss is found in 5–15% of most populations worldwide. Aim. The applicability of salivary β-hexosaminidase (β-HEX A%, percentage of β-HEX A isoenzyme to total β-HEX) and β-HEX B% (β-HEX B/β-HEX) indexes was investigated as a possible marker of periodontitis. Methods. Thirty three alcohol-dependent smokers (AS) and 32 healthy controls (C) were enrolled in the study. The activity of β-HEX was measured spectrophotometrically. Results. β-HEX A% was significantly higher and β-HEX B% was lower in AS than in C group. We found a significant correlation between β-HEX A% and gingival index (GI) and an inverse correlation between β-HEX A% and salivary flow (SF), in all groups. Salivary β-HEX A% index in smoking alcoholics at 0.23 had excellent sensitivity (96%) and specificity (91%); the AUC for β-HEX A% was high (0.937). There were no correlations between amount/duration-time of alcohol drinking/smoking and β-HEX A% or β-HEX B%. We found significant correlations between the time period of denture wearing and GI, papilla bleeding index (PBI), and decayed missing filled teeth index (DMFT) and between GI and the amount of smoked cigarettes per day. Conclusion. Bad periodontal state was most likely due to the nicotine dependence. Salivary β-HEX A% is a promising excellent marker for the diagnosis of periodontitis.

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B), β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.