Effects of excessive alcohol drinking on nicotine biotransformation in rats.

Alcohol and nicotine (tobacco smoke) are often used together, and taking both addictive substances is associated with an increased risk of certain diseases. It is extremely important to understand the pharmacodynamic and pharmacokinetic mechanisms of the interaction between nicotine and ethanol, which are still not fully understood. The study aimed to evaluate the influence of chronic alcohol consumption on nicotine biotransformation in ethanol-preferring and non-preferring male and female rats. Rats were divided into four groups depending on their alcohol preferences and gender. Nicotine, nornicotine, nicotine N-oxide, cotinine, trans-3'-hydroxycotinine, and cotinine N-oxide in rats plasma were determined by LC-MS/MS after five days of exposure to tobacco smoke. A non-compartmental analysis of nicotine and its metabolites was used for pharmacokinetic parameters calculation. Our experimental results showed that the rate of nicotine elimination depends on gender, regardless of alcohol preferences (significantly slower in females than in males). Mean residence timeof nornicotine, cotinine, and trans-3'-hydroxycotinine were significantly higher in alcohol-preferring male rats than in alcohol preferring female rats. In non-alcohol preferring female rats compared to ethanol-preferring female rats, significantly more nicotine N-oxide (fivefold) and trans-3'-hydroxycotinine (twofold) reached the general circulation unchanged. Drinking ethanol influenced the elimination of nornicotine and cotinine in male rats. Ethanol consumption was identified as a modifier of nicotine pharmacokinetics and this was gender-dependent.

Intravenous and oral suicidal e-liquid poisonings with confirmed nicotine and cotinine concentrations.

The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patient's blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison.

Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats.

BACKGROUND: A vast majority of people who abuse alcohol are also defined as "heavy smokers". Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use of both of them. The aim of the study was to evaluate the influence of tobacco smoke xenobiotics on ethanol pharmacokinetics and the level of its metabolites in alcohol preferring and non-preferring rats. METHODS: Ethanol, acetaldehyde, methanol, n-propanol and n-butanol were determined in whole blood by means of gas chromatography. Cotinine in serum was determined by LC-MS/MS. A non-compartmental analysis (cotinine, acetaldehyde) and Widmark equation (ethanol) were used for pharmacokinetic parameters calculation. RESULTS: Ethanol levels were lower in animals exposed to tobacco smoke compared to rats receiving this xenobiotic, without a prior exposure to tobacco smoke. Lower values of the studied pharmacokinetic parameters were observed in the alcohol preferring males compared to the non-alcohol preferring rats. Both n-propanol and n-butanol had higher values of the pharmacokinetic parameters analyzed in the animals exposed to tobacco smoke and ethanol compared to those, which ethanol was administered only once. CONCLUSIONS: An increase in maximum concentration and the area under concentration-time curve for ethanol after its administration to rats preferring alcohol and exposed to tobacco smoke are accompanied by a decrease in the volume of distribution. The changes in the volume of distribution may be caused by an increase in the first-pass effect, in the intestinal tract and/or in the liver. The acetaldehyde elimination rate constant was significantly higher in alcohol-preferring animals.

Aerosolized albuterol sulfate delivery under neonatal ventilatory conditions: in vitro evaluation of a novel ventilator circuit patient interface connector.

BACKGROUND: Aerosolized medications that have been used in infants receiving ventilatory support have not been shown to be effective clinically among the smallest patients. The aim of this study was to characterize the delivery of aerosolized albuterol sulfate in vitro under simulated neonatal ventilatory conditions using a novel ventilator circuit/patient interface connector. METHODS: A Babylog(®) ventilator (VN500(®); Draeger), a novel ventilator circuit/patient interface (VC) connector (Afectair(®); Discovery Laboratories, Inc.), a TwinStar(®) HME (Draeger) low-volume filter, and either a test lung (Draeger) or lung simulator ASL 5000(®) (IngmarMed) were used. Intermittent mandatory ventilation conditions were set to replicate the most typical ventilation conditions for premature infants. Continuous positive airway pressure was also used to measure aerosol delivery with active respiratory drive from the patient. Albuterol sulfate (0.5 mg/mL) was loaded into the drug reservoir of a Misty Finity(®) nebulizer (Airlife(®); Cardinal Health) and connected to the ventilator circuit either via a "T" connector as described by the manufacturer [standard of care (SoC)] or via the VC connector. Albuterol extracted from the filters was analyzed using qualified high-performance liquid chromatography. In addition, a laser diffraction spectrometry (Spraytec(®); Malvern) and white-light spectrometry (Welas model 2100; Palas GmbH) were used to determine particle size distribution (PSD). RESULTS: Compared with SoC, the amount of albuterol delivered using the VC connector was significantly greater (p<0.001) under simulated neonatal ventilatory conditions. Additionally, the PSD profile of albuterol sulfate delivered using the VC connector was more representative of the PSD profile directly from the nebulizer. CONCLUSIONS: The use of the VC connector increased the delivery of albuterol sulfate and resulted in a PSD profile at the patient interface that is more consistent with the PSD profile of the selected nebulizer when compared with SoC. This VC connector may be a useful, new approach for the delivery of aerosolized medications to neonates requiring positive pressure ventilatory support.

[Electronic cigarettes - effects on health. Previous reports]. / Elektroniczne papierosy - wplyw na zdrowie. Dotychczasowe doniesienia.

Currently very popular in the market of tobacco products have gained electronic cigarettes (ang. E-cigarettes). These products are considered to be potentially less harmful in compared to traditional tobacco products. However, current reports indicate that the statements of the producers regarding to the composition of the e- liquids not always are sufficient, and consumers often do not have reliable information on the quality of the product used by them. This paper contain a review of previous reports on the composition of e-cigarettes and their impact on health. Most of the observed health effects was related to symptoms of the respiratory tract, mouth, throat, neurological complications and sensory organs. Particularly hazardous effects of the e-cigarettes were: pneumonia, congestive heart failure, confusion, convulsions, hypotension, aspiration pneumonia, face second-degree burns, blindness, chest pain and rapid heartbeat. In the literature there is no information relating to passive exposure by the aerosols released during e-cigarette smoking. Furthermore, the information regarding to the use of these products in the long term are not also available.

Exposure to alcohol and tobacco smoke causes oxidative stress in rats.

BACKGROUND: Tobacco smoking and alcohol abuse causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Liver is the main organ exposed to alcohol toxic metabolites, whereas tobacco smoke is chiefly harmful to the lungs. METHODS: The aim of the current study was the assessment and comparison of selected oxidative stress markers, reduced glutatione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase, nitrites and protein nitrosylation and DNA damage in the livers and in the lungs of alcohol-addicted rats exposed to tobacco smoke alone or in combination with a single dose of ethanol. RESULTS: The highest levels of GSH were measured in the liver of smoke only exposed animals and in the lungs of rats exposed to smoke and alcohol. In the liver of animals treated with a single dose of alcohol or with smoke and alcohol, GST was significantly higher than in the group exposed to smoke only. SOD and catalase showed the highest activities in the livers of rats receiving a single dose of alcohol. High concentration of nitrites was observed in the lungs of animals treated with smoke and alcohol in combination, which corresponded to elevated protein nitrosylation in this group, whereas in the livers of these animals relatively low level of nitrites was accompanied with the lowest concentration of nitrosylated proteins. In the liver of alcohol only treated rats the highest nitrites corresponded to the highest protein nitrosylation. In the lungs of all treatment groups the range of DNA damage was higher, than the respective values in the livers. Although alcohol is not considered a specific toxicant to the lungs it was found to cause oxidative stress in this organ. CONCLUSIONS: The obtained results suggest that in the ethanol-addicted rats combined exposure to smoke and alcohol differentially modulate endogenous antioxidant defense system and reactions to oxidative stress.

Exposure to ethanol and tobacco smoke in relation to level of PCNA antigen expression in pancreatic and hepatic rat cells.

BACKGROUND: Previous results proved that simultaneous effect of tobacco smoke constituents and alcohol consumption may change toxicity of these substances and have a greater effect on hepatic and pancreatic disease and cancer risk. The aim of this study was to investigate hepatocyte and pancreatic cells regeneration after tobacco and/or ethanol treatment. METHODS: In the study, four groups of rats were used - alcohol non-addicted and addicted male and female rats. The animals from each group were exposed to tobacco smoke, to ethanol or tobacco smoke and ethanol. After the exposure, pancreas and liver were collected at two time-points--5 and 24 h. Biochemical methods were used to measure concentration of ethanol and cotinine in blood and plasma. Additionally, proliferating cell nuclear antigen labeling index (PCNA-LI), an S-phase marker was assessed by immunohistochemical staining and morphometric method. RESULTS: Our experimental results showed that the exposure of rats to tobacco smoke does not have influence on ethanol concentration in blood of non-addicted (male, female) and addicted (male and female) animals. The results also proved that alcohol addiction did not influence nicotine metabolism in all animals exposed to tobacco smoke. Morphological studies of tissues display significant damage in liver of addicted males, including fatty degradation, fibrosis and slight inflammatory infiltrate. Immunohistochemical studies revealed at first, significant increase of PCNA-LI and, thus, increased cell proliferation activity and damage in tissues were observed in hepatic and pancreatic cells of addicted males when compared with non-addicted males. Secondly, comparison between addicted males and addicted females revealed that PCNA-LI in females is significantly lower, both in hepatic and pancreatic tissues. And finally, animals exposed only to ethanol and to tobacco smoke plus ethanol were characterized by higher percentage of PCNA positive cells in relation to animals exposed only to tobacco smoke. CONCLUSION: From the preliminary study one can conclude that the influence of ethanol and simultaneous influence of ethanol and tobacco smoke impairs liver and pancreatic functions to a greater degree than tobacco abuse.

How to combine non-compartmental analysis with the population pharmacokinetics? A study of tobacco smoke's influence on the bioavailability of racemic citalopram in rats.

BACKGROUND: Citalopram (CIT) is an antidepressant drug from the group of selective serotonin reuptake inhibitors in which it is the most potent selective inhibitor of serotonin uptake currently available. Patients treated with CIT are often heavy cigarette smokers. Individual pharmacokinetic parameters cannot be directly estimated if full pharmacokinetic profiles are not available for each subject. Sparse sampling is common to experiments using small animals, such as the case that our study is concerned with. METHODS: The aim of the study was to demonstrate how the two (non-compartmental analysis (NCA) and nonlinear mixed-effect (NLME)) approaches, used simultaneously, can help overcome specific limitations of these separate methods whilst at the same time preserve their respective benefits. RESULTS: Despite the ultra-sparse design, the NLME approach enabled us to develop a pharmacostatistic model with the required covariate--exposition to the tobacco smoke. CONCLUSIONS: A tobacco smoke slows down the absorption of the CIT and at the same time makes it more effective. The consistency of results obtained both with NCA and NLME decreased the risk of model misspecification and increased confidence in the final conclusions. Combining NLME with NCA may therefore be recommended for investigating pharmacokinetic properties of the drug in the sparse designs.

[Valproic acid concentration in the blood serum of pregnant women and umbilical cord blood in relation to the condition of the newborn--case studies]. / Stezenie kwasu walproinowego w surowicy krwi kobiet ciezarnych oraz krwi pepowinowej w odniesieniu do stanu noworodka--analiza przypadków.

Epilepsy is one of the most common neurological diseases in the world. One of the most difficult clinical problems associated with the disease is to treat pregnant women because the use of antiepileptic drugs increase the risk of birth defects in the fetus. The second most common use in pregnant women is an antiepileptic drug valproic acid. Its use is associated with an increased risk of serious birth defects such as neural tube defects, heart defects, cleft palate, urinary tract defects, limb defects, specific syndromes that cause dysmorfizm face or abnormalities of the reproductive organs and developmental disorders affecting cognitive and behavioral functions. To minimize the risk to the fetus can be through the use of contraception and planning for pregnancy, taking valproic acid monotherapy, at a dose of less than 1000 mg/day in 2-3 divided doses, folic acid supplementation, close monitoring during pregnancy and full cooperation with doctors: a gynecologist and neurologist. The aim of this study was to measure the concentrations of valproic acid in maternal serum and cord serum and a reference to the results of the newborn. The concentrations of valproic acid in the serum was performed using high performance liquid chromatography method with fluorometric detection. Valproic acid concentration in the blood serum of patients housed or slightly exceed the therapeutic concentration. In all samples of umbilical cord blood serum were detected, no drug found to have birth defects. Born children should remain under control in order to detect possible birth defects that cannot be detected immediately after birth.

[Tobacco smoking and clinical periodontal status with clinical parameters]. / Palenie tytoniu a stan kliniczny przyzebia z uwzglednieniem wskazników klinicznych.

Increasing evidence points to smoking as a major risk factor for periodontitis and, affecting the prevalence, extentent and severity of the disease. The aim of our study was to asses due to clinical and statistical methods oral health status among a group of 61 patients of Conservative Dentistry and Perodontology Department Poznan University of Medical Sciences according to DMF and CPITN indices, PPD and CAL level. In statistical analysis the Friedmann and Kruskal Wallis test were used.

[Physiological metals in the serum, hair and nails of patients with head and neck cancer]. / Metale fizjologiczne w surowicy, we wlosach i paznokciach pacjentów z nowotworami w obrebie glowy i szyi.

Cigarette smoking and excessive alcohol drinking result in the rise of numbers of patients suffering from the head and neck cancer. Addiction to any of these stimulants carry a risk of developing a cancerogenesis process. Using them simultaniously lead not to a summary of each of those risks but multiplies them. Scientific research also indicates the important difference in the incidence of cancer in people who have never smoked cigarettes or drunk alcohol in comparison to those, whose exposure to these stimulatns was longterm - in such case, the former group had a lower percentage of developing the disease. Human body burdened with the ongoing cancer shows disturbances on various levels of the system. One of such disturbances is change of the concetration levels of physiological metals, such as calcium, magnesium, iron, copper, zinc or mangenese. They play key roles in maintaing the hormonal and ionic stability, they act as cofactors in many enzymes in metabolic processes. Diagnostic research of any deviations in levels of those essential elements enables a full estimation of a patient condition. The aim of this study was physiological metal levels evaluation in different kinds of biological material in patients with tumors of larynx, salivary glands and oral cavity and tongue. Hair and nail samples were used as examples of alternative material, beside the serum samples, which is a standard material and often used. Subjects were patients of Otolaryngology and Laryngological Oncology Clinic of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu) and The Head and Neck Surgery Ward of The Greater Poland Cancer Centre in Poznan. Subjects were 41 men and 18 women with tumors of larynx, salivary glands and oral cavity and tongue. The control group consisted of patients from the Otolaryngology and Laryngological Oncology Clinic of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu), The Head and Neck Surgery Ward of The Greater Poland Cancer Centre in Poznan and patients of Department of Endocrinology, Metabolism and Internal Medicine of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu) and Department of Conservative Dentistry and Periodontology Poznan University of Medical Sciences. They gave answers to the questionnaire concerning smoking habits, alcohol consumption and dietary habits, Then the samples of their serum, hair and nails were collected. After careful preparations the biological material has underwent the process of digestion, and then calcium, magnesium, iron, copper, zinc, mangenese were determined quantitatively using the method of ICP-MS. Profile of the patients who took part in the research displayed a strong correlation between tobacco smoking with alcohol drinking and appearance of larynx, salivary gland and oral cavity and tongue cancer as well as between exclusively tobacco smoking and appearance of these types of cancer. There is a higher incidence of larynx, salivary gland and oral cavity and tongue cancer when there is a deficiency of grain products or fibre in everyday diet. A higher level of calcium, magnesium, iron and manganese was found in patients' hair and nails who suffered from salivary gland cancer. According to applied Chemometric Analysis of Principal Component 1 - concentrations of iron, copper and manganese with magnesium and zinc in patients' nail samples showed strong correlation between measured variables. In patiens' hair samples measured correlation between variables was decreased - concentrations of calcium and magnesium as well as of iron and manganese were highlighted as two groups of variables which showed some correlation in this type of biological material. Further research is required to indicate which of alternative biological materials - hair or nail samples - in relation to serum, would provide a better evaluation of physiological metal levels.

[The influence of periodontal diseases on the concentration of selected metals in saliva]. / Wplyw chorób przyzebia na stezenie wybranych metali w slinie.

Analysis of elements (mainly metals) in biological materials provides a challenge for analytics. It results from complex matrix of this kind of samples and strict requirements for purity at all stages of the analytical process. Over the years many effective methods for determination of metals in body fluids have been developed, which link with searching for the association between elemental composition of human body and various diseases. The aim of the investigation was to study the usefulness of available methodology to determination of selected metals in saliva and blood of patients with periodontitis and healthy controls by two techniques" ICP-MS and ICP-OES. Next statistical analysis of the data statistical was carried out. The influence of periodontal disease upon the concentrations of selected metals (Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Pb and Zn) in saliva was examined, as well the attempt to classify samples of patients with periodontitis and healthy individuals correctly was made. Additionally mutual relations between analytes in examined materials were determined by computing the Pearson's correlation coefficient and principal component analysis (PCA).

[Saliva cotinine determination using high-performance liquid chromatography with diode - array detection]. / Oznaczanie kotyniny w slinie metoda wysokosprawnej chromatografii cieczowej z detekcja diodowa.

The use of tobacco is a very serious threat to public health. Reducing the proportion of smokers easily leads to improved health of the general population. Smoking is a proven risk factor for respiratory disease, cardiovascular disease and cancer and complications during pregnancy. To verify the level of exposure to tobacco smoke in most patients used a simple test markers of exposure. The most commonly used marker in the evaluation of exposure to tobacco products is cotinine, which is a major metabolite of nicotine contained in tobacco smoke. Biological material most commonly used in this type of study is blood, urine and saliva. In the present study Sarstedt Salivette tubes were used to samples collection. In order to determine the concentration of cotinine in saliva samples analyzed with high performance liquid chromatography with diode array detection after extraction of cotinine from saliva by solid phase extraction. The method was linear of 10 to 400 ng/ml. The limit of detection was the value of the signal-to-noise ratio S/N=3, it amounted to 6 ng/ml, the limit of quantification was 10 ng/ml. The intraday repeatability was 8% for lowconcentrations, for high concentrations - 3.7%. Reproducibility interdays for low concentrations was 2.4%, for high concentrations - 4.1%. We analyzed 18 samples of saliva derived from patients smoking volunteers from the Department of Conservative Dentistry and Periodontology, University of Medical Sciences. University of Medical Sciences and the Chair and Department of Endocrinology, Metabolism and Internal Medicine, University of Medical Sciences. University of Medical Sciences. Mean concentrations of cotinine in patients was 240.9 ng/ml of saliva. In this study we demonstrated the usefulness of the saliva cotinine determination method in the assessment of patient exposure to tobacco smoke.

[Selected biochemical parameters of oxidative stress as a result of exposure to tobacco smoke in animals addicted to ethyl alcohol]. / Wybrane parametry biochemiczne stresu oksydacyjnego w wyniku ekspozycji na dym tytoniowy zwierzat uzaleznionych od alkoholu etylowego.

Smoking cigarettes and alcohol addiction are serious problems in health hazard and life of society. Tobacco smoke leads to many kinds of cancer formation and scientific research indicates, that heart-vascular disease and lung cancer are the most common diseases caused by tobacco smoke. While talking about ethanol, it is responsible for liver, pancreas, mucous membrane damage and leads to central and circular nervous disorder. Scientific research indicates, that many smokers drink alcohol and vice versa. Unfortunately in that case the risk of many diseases increases. Both of these stimulants leads to enlarged production of reactive oxygen species, which is connected with unbalance between pro and antioxidant processes in human organism. Free radicals in normal conditions plays positive role but with tobacco smoke and alcohol connection may lead to serious changes in human organism. They damage organs, it comes to protein structure, nucleic acid and fat violation, which in consequence leads to immunity decrease and many pathological changes. Reactive oxygen species also plays role in pathogenesis of many diseases: diabetes mellitus, atherosclerosis and Down syndrome. ROS may also increase the risk of pancreas, lung, larynx and urinary bladder cancer formation. Human organism defends oneself from harmful influence of reactive oxygen species owing to enzymatic and non-enzymatic systems presence-Non-enzymatic antioxidants: glutathione, carotene, bilirubin, tocopherol, uric acid and ions metals temporary complex belong to non-enzymatic systems. To enzymatic ones belong: catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase. The aim of the study was tobacco smoke and ethyl alcohol influence evaluation in rats addicted to these substances on activity of chosen enzymes responsible for organism defense against toxic compounds action. To this study 63 white, Wistar tribe rats at the age of 3,5 months were used - males addicted to ethyl alcohol. They were divided into 3 groups, each consist of 21 rats. Animals of Group I were exposed on harmful tobacco smoke influence. Group II constitute animals, which were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. The next Group - III, in which animals at first were exposed on tobacco smoke influence. When exposition was over, animals were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. Depending on the type of marker and studied organ, changes in the levels of selected enzymes, responsible for defending organism against reactive forms of oxygen has been shown. Both tobacco smoke and ethyl alcohol resulted in a change of glutathione levels in the serum and tissues of animals. Tobacco smoke has the biggest influence on protein nitrozylation in the brain and ethyl alcohol had influence on glutathione level in serum, kidney, brain and superoxide dismutase activity in the brain. Application of many oxidative stress markers allows for evaluation of its differential influence on various organs.

[Development and validation of method for the determination of cynarin, luteolin in plasma]. / Opracowanie i walidacja metody oznaczania cynaryny, luteoliny w osoczu.

The aim of this study was to develop and validate the method of cynarin and luteolin, the main constituents of artichoke (Cynara scolymus L.) leaf extract, determination in plasma. The compounds were separated using the high-performance liquid chromatography technique with diode array detection (HPLC-DAD). The analysis was preceded by liquid-liquid extraction using as the extracting agent ethyl acetate. The HPLC separation was performed on C18 column under gradient conditions using a mobile phase - 0,05% trifluoroacetic acid in water and methanol. The detector was set at lambda=330 nm. The validation was related to linearity, sensitivity (LOD and LOQ), accuracy and repeatability. In the validated method the linearity was achieved within concentration range 1,5625 - 50,0 microg/cm3 for the cynarin (R2=0,9989) and 1,5625 - 200,0 microg/cm3 for the luteolin (R2=0998). The limits of detection for cynarin and luteolin was: 0,75 microg/cm3 and 0,1 microg/cm3 and the limits of quatification: 2,25 microg/cm3 and 0,2 microg/cm3, respectively. Coefficient of variation for the inter-day and the intra-day analysis, which is a precision and accuracy parameter, do not exceed 10%. Recovery was 67% for the cynarin and 96% for the luteolin. The practical application of this method was proved by analysis of plasma samples from rats. The animals were administrated artichoke leaf extract - orally and intraperitoneally at a dose of 3 g/kg body weight or pure substances - intraperitoneally at a dose 1 mg/kg of luteolin and 0,5 mg/kg of cynarin. The presence of investigated compounds was proved only in samples after intraperitoneal administration of pure substances. The developed method is used to determine simultaneously cynarin and luteolin, after intraperitoneal administration of pure compounds.

[Artichoke--herbal drug]. / Karczoch zwyczajny--lek roslinny.

The liver is the gland most vulnerable to the toxic effects of xenobiotics, as responsible for their metabolism. Significant impact on the functioning of this gland has a style of life: alcohol consumption, diet with high fats ingredients and prooxidative substances and synthetic drugs. Very improtant aspect in herbal medicaments is protective properties on parenchymal organ-damaging. Concomitant intake of plant extracts containing cytoprotective compounds, may increase the efficacy of treatment and reduce side effects. One of the plants of the hepatoprotective action is artichoke (Cynara scolymus L.). Artichoke with multiple therapeutic properties and practically no side effects is recommended not only in disorders of the liver, but also in the prevention of atherosclerosis and hyperlipidemia or dyspeptic disorders.

[Artichoke--untapped potential of herbal medicine in the treatment of atherosclerosis and liver diseases]. / Karczoch zwyczajny- niewykorzystane mozliwosci leku roslinnego w terapii miazdzycy i chorób watroby.

Substances of natural origin are the subject of growing interest on the part of both researchers and doctors. One of the well known herbal medicines extensively examined in terms of clinical and pharmacological is artichoke (Cynara scolymus L.), which was used in European medicine from the 18th century. His multidirectional treatment is a documented fact and it is associated with treatment of dyspepsia, influence of active substances contained in artichoke on plasma lipid levels and with a strong antioxidant effect of the artichoke extract--due to this properties, artichoke compounds have a protective effect on liver cells.

[Effect of tobacco smoke on lipids peroxidation and liver function in streptozotocin diabetic rats--preliminary study]. / Wplyw dymu tytoniu na peroksydacje lipidów i funkcje watroby u szczurów z cukrzyca streptozotocynowa--badania wstepne.

Diabetes is considered a group of diseases with chronic hyperglycemia caused by various organ disorders, failure or damage as a common feature. Hyperglycemia exerts toxic effect on endothelium, promotes oxidative stress, inhibits bioavailability of nitrogen monoxide (NO) and leads to formation of advanced glycation end products. Moreover, hyperglycemia induces production of reactive oxygen specimens (ROS) through several distinct mechanisms, such as: glucose autoxydation activation of polyol (sorbitol-aldose reductase) pathway, non-enzymatic glycation and neutrophil granulocyte's stimulation. These changes lead to uncontrolled oxidation and peroxidation of lipids, nucleic acids, certain enzymes and most of all--oxidative protein damage (OPD) in many tissues. The aim of this study was to evaluate influence of exposure to tobacco smoke on lipid peroxidation and liver function in experimentally induced diabetes. The research showed that the protein level in blood serum did not change neither in case of induced diabetes nor after tobacco smoke exposure. However a statistically significant increase of lipid peroxidation was observed in rats with pharmacologically induced diabetes. In animals exposed to tobacco smoke only lipid peroxidation increasing trend was demonstrated, while in animals with induced diabetes and exposed to tobacco smoke a statistically significant decrease of lipid peroxidation was noticed. In the adopted experimental model basically no alterations of hepatic aminotranspherases were observed, with exception of AIAT in the group of diabetic animals compared to rats in the control group. Results of the study do not explicitly explain the influence of tobacco smoking in experimentally induced diabetes on lipid peroxidation and liver functions.

[Develop rapid and inexpensive method for the determination of methadone and its major metabolites for monitoring therapy]. / Opracowanie metody oznaczania metadonu w surowicy dla potrzeb terapii monitorowanej.

Methadone maintenance therapy is one of the most popular treatments for opiate addiction. The easiest and the most reliable way to monitor the accuracy of the therapy is determination of methadone and its metabolites in biological material. The aim of this study was to develop rapid and inexpensive method for the determination of methadone and its major metabolites--EDDP and methandol in drug concentration monitoring therapy and to check its suitability to real samples collected from the patients, who participated in methadone maintenance therapy. The method is characterized by a wide range of linearity--from 50 to 1000 ng/ml for methadone and methadole, and from 20 to 600 ng/ml for EDDP. The lower limit of quantification for methadone and methadole was 50 ng/ml and for 20 ng/ml for EDDP. The repeatability of the method during the day and between days is below 10%. The method allows the determination of minimum concentrations of methadone (before the next dose) in patients treated with standard doses (40-120 mg/day) of this medicine. Different concentration ratios of metabolites to parent drug prove that the polymorphic metabolism leads both to the EDDP, methadone and methadole.

[Development of analytical method for determination nicotine metabolites in urine]. / Opracowanie metody oznaczanie metabolitów nikotyny w moczu.

The assay of biomarkers in biological material is the most popular and reliable method in estimate exposure to tobacco smoke. Nicotine and its metabolites qualify to the most specific biomarkers for tobacco smoke. Currently the most often used are cotinine and trans-3'-hydroxycotinine. The aim of this study was development of easy and quick method of determining nicotine and its main metabolites with high performance liquid chromatography--available in most laboratories. Nicotine and its metabolites in urine (cotinine, trans-3'-hydroxycotinine, nornicotine and nicotine N-oxide) was determined by means of high performance liquid chromatography with spectrometry detection (HPLC-UV). The determined compounds were extracted from urine by means of the liquid-liquid technique, before analysed by the HPLC method. Developed technique of high performance liquid chromatography proved to be useful to assessment nicotine and its four metabolites in smokers, though further research are necessary. The further modification of procedure is required, because of the interferences of cotinine N-oxide with matrix, which prevent determination. Increasing the efficiency of extraction nicotine and nornicotine could enable the determination in people exposed on environmental tobacco smoke (ETS). This study confirm other authors' observations that 3'-hydroxycotinine might be equivalent with cotinine predictor of tobacco smoke exposure, however further studies are required.