Search

This study aimed to evaluate the impact of nicotine and other xenobiotics contained in tobacco smoke on the pharmacokinetics of ethyl alcohol and on the levels of toxic ethanol metabolites such as acetic aldehyde.We also sought to evaluate the impact of a one-time administration of ethyl alcohol on the biotransformation of nicotine, the addictive alkaloid of tobacco smoke, to its main metabolite, cotinine. Rats were divided in three groups. The first group was exposed to tobacco smoke (6 h per day, for 5 days), the second group was treated with alcohol (2 g/kg), and the third group was exposed to tobacco smoke and treated with alcohol. Earlier exposure to tobacco smoke had an insignificant impact on the elimination of alcohol, but caused a significant increase in the volume of distribution, which could be caused by an increase in the first-pass effect. In contrast, inhaling tobacco smoke decreased acetic aldehyde concentrations in the first hour after alcohol administration. The major finding of this study was that a single dose of ethyl alcohol increases the rate of elimination of cotinine, the major metabolite of nicotine. This was demonstrated by a reduced biological half-life (t(0.5)) and mean resident time (MRT).

Four different approaches to population pharmacokinetic analysis were applied to routine clinical data on carbamazepine intoxications in epileptic and alcoholic patients. The computational issues were noticed for maximum likelihood based methods, while Markov Chain Monte Carlo approach revealed that the estimates of absorption and lag parameters might be unreliable. Non-identifiability of these parameters may be the source of computational problems with other methods. Simultaneous use of different approaches to population pharmacokinetics is therefore advised, since it allows for verification of the obtained results.

Numerous studies warn that women who smoke can suffer from weakened functioning of their ovaries and disturbed synthesis and metabolism of hormones. This may cause many pregnancy complications or premature menopause and osteoporosis. Moreover, smoking disturbs the menstrual cycle, decreases the effectiveness and increases the undesirable effects of the hormone replacement therapy. Tobacco smoke disturbs gametogenesis, ovulation, Fallopian tube transport, fertilization and the implantation of a fertilized cell, which results in the reduction of fertility. The goal of the present thesis was a toxicological assessment of the influence of tobacco smoke on the level of luteinizing hormone, follicle stimulating hormone, progesterone, and estradiol in blood serum of female rats, taking into consideration the phases of their sexual cycle. The experiment utilized a cytological method of determining the phases of the sexual cycle, which enabled the researcher to divide the rats into two groups (exposed to tobacco smoke and unexposed). Each of the groups was further divided into four subgroups with six animals for each phase of the sexual cycle (Proestrus, Estrus, Metestrus, Diestrus). The rats from the first group were exposed to tobacco smoke with the concentration of 1500 mg of Carbon Monoxide (CO) per cubic meter of ambient air (per content of Carbon Monoxide) for 5 days for 6 hours a day. Every day before the exposition at the same time the phases of the sexual cycle of female rats were checked in all of the subgroups. On the last 5th day of the experiment, after the exposition to the smoke, smear tests were conducted. The unexposed group was the control group. The evaluation of the exposition of the animals to tobacco smoke was based on the determination of the level of cotinine in blood serum by ELISA method. The measurement of the concentration of hormones was conducted by means of a jurisdiction method of electrochemiluminescence. In the experiment, a statistical difference was observed between the concentration of cotinine in the blood serum of the animals that were in the Proesrtus phase (86.8 ng/ ml), compared to the group in the Metestrus phase (351.0 ng/ml) and Diestrus phase (304.6 ng/ml). In the experiment a very high level of progesterone concentration was marked in the blood serum of the female rats that were exposed to tobacco smoke and that were in the Proestrus phase (195.1 ng/ml). The level of progesterone among the animals exposed to cigarette smoke was statistically higher compared to the control group (99.1 ng/ml). In all probability, this was caused by the slower metabolism of nicotine or faster biotransformation of cotinine. The experiment confirmed the negative influence of cigarette smoke on the course of the sexual cycle. The sexual cycle of the female rats exposed to tobacco smoke changed its rhythm and kept its proper course only in 29% of the examined animals.

The article summarise the current knowledge about medicaments used in smoking cessation. In detail are discussed drugs, which are the first choice in treatment of nicotine dependence. The basic preparations of Nicotine Replacement Therapy (NRT) are: chewing gum with nicotine which allowed for instantaneous reaction on craving for nicotine, and nicotine patches which supplement organism with this alkaloid with constant rate. The efficacy of other NRT preparations (vapour inhaler, nasal spray, sublingual tablet, lozenge) are on the some level as nicotine chewing gums and nicotine patches. Alternatives for NRT are two drugs bupropion and varenicline. Both drugs are effective in treatment the nicotine dependence and as well as nicotine containing medicaments can be us as a first line drugs. The efficacy of other drugs (nortryptyline, mecalamine, clonidine) have not been proved in randomized controlled studies.

Determination of xenobiotics in hair has become common in evaluation of exposure to drugs. It can be used to assess the drug intake among adults and exposure to these substances in prenatal period. The aim of this study was the nicotine determination in hair of newborns' whose mothers were smoking during pregnancy. Also the relationship between concentration of cotinine--the main metabolite of nicotine in the urine of mothers and nicotine concentration in their infants' hair has been evaluated. The group of 15 women who had been smoking during pregnancy and 10 non-smoking and not exposed to ETS women and their newborns were the subject of the study. The cotinine levels in maternal urine samples was measured by the high performance liquid chromatography (HPLC) with a spectrometric detection, with the use of norephedryne as an internal standard, after a prior extraction with the use of liquid-liquid technique. Nicotine assess in infants' hair was carried out by means of gas chromatography coupled with mass spectrometry, with the use of ketamine as an interior standard, after the prior extraction with the use of liquid-liquid technique. The mean cotinine concentration in the group of smoking women amounted to 1132.5+/-1236.3 ng/mg creatinine and the level of nicotine in hair of children amounted to 1.9+/-3.2 ng/mg of hair. In the group of non-smoking women the urine cotinine test showed that two patients were exposed to the tobacco smoke. Nicotine in their children's hair was below the detection limit. The demonstrated correlation between the nicotine concentration in infants' hair and the cotinine levels in mothers' urine shows that the source of fetal exposure to tobacco smoke constituents is smoking during pregnancy. The applied gas chromatography method/mass spectrometry method allows to evaluate the level of nicotine in hair of the newborns, whose mothers were smoking during pregnancy, however it seems that in the case of exposure to ETS a more sensitive method, such as gas or liquid chromatography coupled with tandem mass spectrometry has to be applied.

Smoking in a workplace can be an important source of the exposure to environmental tobacco smoke (ETS). Harmful effect of ETS on the human health is well proved phenomenon. Exposure to ETS increases the risk of the cardiovascular diseases, the respiratory symptoms and illnesses, and the lung cancer. The installation of the ventilation and filtration systems or separation of smokers and non-smokers decrease the exposure to ETS but do not solve the problem. One reasonable and economically justified solution is complete restriction of tobacco smoke in closed area of the workplaces.

To assess the exposure to tobacco smoke constituents, the biomarkers are used. In most studies conducted among active smokers, the cotinine is usually utilised as such a biomarker. The aim of this study was to estimate an application of determining two nicotine metabolites, cotinine and trans-3'-hydroxycotinine (3-HC) in order to assess cigarette smoking among pregnant women. There were 25 patients (15 smokers, 10 non-smokers) admitted to Delivery Ward in Gynecology and Obstetrics Clinical Hospital of the University of Medical Sciences in Poznan. The free and total form of cotinine and trans-3'-hydroxycotinine in urine were determined by the means of high performance liquid chromatography with spectrometry detection. The results of this studies indicated that in urine both cotinine and trans-3'-hydroxycotinine are conjugated with glucoronide acid in the high degree. The linear correlation between free and conjugated form of cotinine and whole cotinine concentration indicates the possibility of application of all three of them as biomarkers of tobacco smoke exposure. The high conjugation of trans-3'-hydroxycotinine with glucuronic acid (over 80 %), and high correlation between glucuronide and total trans-3'-hydroxycotinine concentration proves necessity of having the urine samples hydrolysed or determining the 3'-hydroxycotinine glucoronide, when application of 3-HC as a biomarker of tobacco smoke exposure is concerned. Our studies confirm other authors' observations that division of 3'-hydroxycotinine and cotinine concentrations might be used as a predictor of differences in cotinine metabolite ratio (polimorphism). The studies shown that using analytical equipment, nowadays available in the most laboratories (HPLC), it is possible to determined two biomarkers which are very useful and give various information, no matter whether they are conjugated with glucuronic acid, or not.

Verification of the results of questionnaire studies of exposure to tobacco smoke require determination of the biomarkers in body fluids. For performing such measurements the fast and simple method is needed. The aim of this study was to estimate usefulness of enzyme-linked immunosorbent assay (ELISA) in routine cotinine determination in urine of active smokers and compare it with reference high performance liquid chromatography method (HPLC). In the study participated 15 non smoking and 15 smoking women. In the urine of tese women cotinine concentration of cotinine was measured by the means of HPLC and ELISA methods. The ELISA method, used in quantity measurement of cotinine in urine, is of great accuracy, sensitivity and specificity which were proved by comparison with high performance liquid chromatography (HPLC) reference method. Number of false positive and false negative results obtained by ELISA method did not exceed 10%. A high correlation coefficient, r=0.9056, between results of determining cotinine in urine by means of ELISA and HPLC methods, confirmed the utility of ELISA method to estimate the tobacco smoke exposure. The differences in cotinine concentration values obtained by ELISA and HPLC methods did not depend on cotinine concentrations in the urine samples. Although numerous advantages of ELISA method used to detect and determine cotinine, it should be taken into consideration that results might be overestimated and cross-reactivity with other xenobiotics present in urine must be concern.

Introduction: Orbitopathy associated with Graves' disease TAO (thyroid associated orbitopathy) is likewise connected with environmental factors including tobacco smoking. Tobacco smoking increases the risk of ophthalmologic pathology and leads to the orbital tissue damage due to the hypoxia. The aim of the study was to correlate the concentration of urinecotinine (marker of tobacco smoking) in Graves' disease patients with TAO with points received on the Fagerström questionnaire., Materials and Methods: Thirty women with different degree of exacerbation of TAO in Graves' disease (34.28 +/- 12.04 yr.) were examined. As control we used 29 women with Graves' disease without TAO (29.35 +/- 12.33 yr.). The diagnosis was established according to level of TSH and level of thyrotropin receptor antibodies (TRAb). Measure of tobacco smoking or exposure to second hand tobacco smoke ETS (environmental tobacco smoke) carried out according to the Fagerström questionnaire, and measured cotinine level (the major metabolite of nicotine in urine). The level of clinical ophtalmopathy was measured according to the CAS (Clinical Activity Score) scale and degree of progression of TAO according to American Thyroid Association (NOSPECS scale). Additionally increase of exophthalmus was measured using the Hertl's exophthalmometer., Results: In the group with TAO: 19 (63.3%) persons had mild exophthalmos (according to CAS), medium in 13 (43.3%) patients, and pronounced exophthalmous in 10 (33%) patients. There was statistically significant difference in the level of TRAb (18.4 +/- 8.2 vs. 5.1 +/- 3.4 IU/l; p < 0.0001) between TAO and controls. There was no correlation between TSH (0.6 +/- 0.02 vs. 0.4 +/- 0.04; p = 0.18) and fT4 (38.8 +/- 29.3 vs. 26.1 +/- 17.3; p = 0.026) in both analyzed groups. Smokers and non-smokers with TAO had no statistically significant in level of TRAb (Mann-Whitney test p = 0.16). No correlation was found between smoking tobacco (cotinine level) and the level of TRAb in patients with TAO (Pearson r = 0.28 p = 0.58). There was a statistically significant difference between the level of urine cotinine in smoking patients with TAO in the highest level of ophthalmopathy exacerbation (> 24 mm; > or = 4 points according to CAS) and those without TAO (Mann-Whitney's test p = 0.04)., Conclusions: 1. In patients with Graves' disease with TAO the highest score of tobacco smoking has been found in persons with the highest ophthalmopathy exacerbation. 2. Estimation of cotinine concentration in urine is the most objective and useful method of tobacco smoking.

In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplementation. Sixty-six pregnant women in the Czerwiakowski Hospital in Kraków were assessed for prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty-two and fifty-eight women were also assessed for postpartum depressive symptoms (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after delivery, respectively. Serum zinc and magnesium levels were also determined at these time points, however, the number of examined subjects were diminished. A significantly higher EPDRS score (by 45%), indicating severity of depressive symptoms, was found on the 3rd day after childbirth compared with the 30th postpartum day. Moreover, the early post-delivery period (3rd day) was characterized by a 24% lower serum zinc concentration than that found on the 30th day after childbirth. BDI scores assessed a month before childbirth revealed mild depressive symptoms, which was accompanied by a serum zinc concentration similar to that found on the 3rd day after delivery. No significant alterations were found in the magnesium levels between these time points. The present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc (but not magnesium) concentration in a very specific type of affective disorder, the postpartum depression.

Acute intoxication with valproic acid is increasingly being observed in clinical practice. In Poland, such intoxication frequently occurs as a result of mixing different drugs or alcohol. We studied the pharmacokinetics of valproic acid in five intoxicated patients. Apart from valproic acid, barbiturates, chlorprotixene, tricyclic antidepressants, tetrahydrocannabinols and alcohol were detected and measured. The absorption of the drug was rapid and the maximum concentration was observed after the period of 3.5-5.6 hr. The lowering of the valproic acid level in plasma was biphasic, with terminal half-life ranging between 8.8-30.9 hr. The calculated apparent volume of distribution was 0.17-0.72 l/kg and could be affected by varied levels of doses as well as time of drug intake (data from interviews of patients) used for calculation and reduction in plasma protein binding at higher concentration of valproic acid. Frequent multiple drug poisonings oblige toxicological laboratories not only to monitor valproic acid concentration in serum, but also to perform the toxicological screenings.

Electroconvulsive seizures (ECS), one of the most effective treatments of depression, induce mossy fiber sprouting (when assayed by means of synaptic zinc method), and this indicates an increase in the synaptic zinc level in the hippocampus following such therapy. The aim of the present study was to investigate the influence of acute and chronic zinc hydroaspartate administration on the synaptic and total zinc level in the rat hippocampus. We used two methods of zinc determination: (1) zinc-selenium method, which images the pool of synaptic zinc, and (2) flame atomic absorption spectrometry, which assays the total concentration of zinc. Our results indicate that chronic (14 x 65 mg/kg), but not acute, zinc hydroaspartate administration intraperitoneally (i.p.) increases the pool of synaptic zinc in the majority of rat hippocampal layers (by 72-190%), except for the stratum moleculare and stratum radiatum CA, and perforant path DG. On the other hand, no changes were found in total hippocampal zinc level, measured by flame atomic absorption spectrometry. These data suggest that chronic zinc treatment increases the pool of synaptic zinc in the hippocampus, and this effect is similar to that observed following chronic ECS treatment. The measurement of zinc concentration in the whole hippocampus by the flame atomic absorption spectrometry method is not sensitive enough to detect such subtle alteration.

Interleukin-1 and interleukin-6 are principal cytokines involved in regulation of expression of acute-phase proteins. In the joint action of both cytokines IL-1 can suppress or enhance the IL-6-dependent induction of gene expression. Here, we report changes in the transcriptome profile of HepG2 cells exposed to IL-6 alone, or IL-1 and IL-6. Cytokine-responsive genes were identified by differential display analysis. Validation of observed changes in the transcript level was carried out using the slot blot method. Out of 88 cDNA species modulated by IL-6, only 38 represent different known genes whereas 18 clones match genomic clones in NCBI data with hypothetical cDNA sequences (the remaining 32 clones showed no homology with the database or represented several clones of the same gene). In the experiments with HepG2 cells prestimulated for 3 h with IL-1 and then stimulated with IL-6, 43 cDNA fragments were amplified. Twenty-three of them represent known genes while 10 clones have inserts matching hypothetical cDNA sequences in NCBI data. The identified transcripts modulated by IL-6 or both cytokines in HepG2 cells code for intracellular proteins of various function. The largest groups represent genes engaged in metabolism, protein synthesis and signaling pathways. Among all genes identified as differentially regulated under stimulation by IL-6, or IL-1/IL-6, six were detected in both types of stimulation. None of the typical genes coding for plasma acute phase proteins was identified in our experiments. This indicates that differential display cannot be used to characterize the profile of a given transcriptome. On the other hand, it is a useful technique for detection of new genes responding to IL-6 alone or IL-6 in combination with IL-1.

The purpose of the study was to measure the concentration of lead and cadmium in urine of women who smoked, were exposed to environmental tobacco smoke (ETS) and were unexposed during pregnancy. The correlations between exposition to tobacco smoke and socioeconomic factors, course of pregnancy and health status of newborns were estimated. The subjects of the study were 231 pregnant women. Information about exposition to tobacco smoke, socioeconomic state, course of pregnancy and health status of newborns was collected from self-created questionnaire. The estimation of tobacco smoke exposition of the women was based on the questionnaire data and their urine cotinine concentration. The urine concentration of lead and cadmium was measured by atomic absorption spectrometry with graphite furnace. The mean urine lead concentration of women who smoked, were exposed to ETS and unexposed to tobacco smoke during pregnancy were respectively: 38.2 +/- 59.1; 36.2 +/- 50.1; 32.7 +/- 53.5 ng/ mg of creatinine, and mean cadmium concentration were respectively: 1.9 +/- 1.6; 1.1 +/- 1.2; 1.3 +/- 1.5 ng/mg of creatinine. The correlation between the urine concentration of cadmium and cotinine was statistically significant. Increased frequency of tobacco smoking was in the group of the women aged less than 25 years, that finished primary or vocational school, had monthly income less tan 500 zł/family member, and have smoking partners. In the group of women who smoked during pregnancy the childbirth was statistically more often by caesarian and supported delivery. The newborns of mothers who smoked and were exposed to ETS had birth weight respectively 348.5 g and 281.1 g smaller than newborns of unexposed mothers. The length of newborns of smoking and ETS exposed mothers were respectively 2.8 cm and 0.7 cm shorter then newborns of unexposed mothers.

From among 4200 chemical compounds contained in the tobacco smoke, nicotine and carbon monoxide are responsible for changes in the heart-vessel system to the greatest extent. Additionally, other toxic compounds, including the carcinogenic ones, have a significant impact on the biological activity in the tissues of blood vessels. A particularly complex picture of the detrimental impact of the tobacco smoke is presented in case of pregnant women, fetuses and newborns. The aim of the research was to assess the impact of tobacco smoke on the permeability of capillaries in different tissues of rats (lungs, brain, liver, kidneys) and testing of the potentially protective impact of rutine (3-rutinozide of quercetin). The research on the permeability of capillaries has been carried out applying Evans blue. The animals were divided into 8 research groups: pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke", and non-pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke". In the first stage of research (pregnant, non-pregnant-- groups: "rutine" and "rutine+tobacco smoke"), the water rutine solution in a dose of 40 mg/kg of body weight was administered. The non-pregnant and pregnant animals from groups "tobacco smoke" and "rutine+tobacco smoke" were exposed to tobacco smoke via inhalation (1500 mg CO/m3 of air) for 21 days. All the animals were injected with the water Evans blue solution in a dose of 30 mg/kg of body weight. After 30 minutes, the animals were killed by cutting the abdominal aorta, and lungs, brain, liver and kidneys were taken for further testing. The cotinine in the urine was determined by the HPLC method, using norephedrine as the internal standard, after the preceding extraction by means of the liquid-liquid technique. The concentration of cotinine in case of non-pregnant and pregnant females was respectively 11.8 +/- 1.9 pg/ml of urine and 12.0 +/- 2.5 microg/ml of urine. In case of the rats, which received the rutine, the concentration of rutine in the group of non-pregnant females was 9.3 +/- 1.0 microg/ml of urine, and in the group of the pregnant ones 8.5 +/- 1.1 microg/ml of urine. In the lungs of non-pregnant animals exposed to tobacco smoke, the decreased permeability of vessels for the albumin-Evans blue complex was proven. The administration of rutine to non-pregnant and pregnant animals did not exert influence on the permeability of vessels in lungs. A similar result was obtained for the lungs of rats receiving the rutine, as well as those exposed to tobacco smoke. In the brain tissue of non-pregnant and pregnant animals, a slight decrease in the content of Evans blue was declared as a consequence of tobacco smoke impact. In the groups receiving the rutine, this flavonoid was declared to influence the blood supply of the brain tissue, and the permeability of the vascular walls. In the liver tissue of animals inhaling the tobacco smoke, the permeability of vascular walls for albumin-Evans blue complex was increased. The rutine did not affect significantly the permeability of vessels, whereas the exposure of pregnant females, which received rutine, to smoke decreased the content of Evans blue in the liver tissue. In the tissues of all tested females, no significant differences between the control groups and groups exposed to tobacco smoke as well as rutine+tobacco smoke were detected. The obtained results do not indicate, however, that in case of chronic exposure to tobacco smoke, the rutine has insignificant protective meaning.

An important problem, particularly from the point of view of the medicine, is active tobacco smoking and passive exposure to tobacco smoke of pregnant women and unfavourable health aftermath for the foetus and a newborns resulting from this. The aim of this study was to evaluate the exposure of smoking mothers to tobacco-specific N-nitrosamines, through the measurement of 4-(metylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine. The evaluation of tobacco smoking was performed on the basis of questionnaire studies and determination of cotinine in urine. The questionnaire studies that have been carried out, allowed the patients to be divided into two groups: women who do not smoke and are not exposed to ETS (17 women), and the ones who smoke (14 women). The women who smoked 11-15 cigarettes a day and more than 16 cigarettes constituted the largest percentage. The conformance of the declaration with the real exposure to tobacco smoke within the group of non-smoking women was 88%. Within the group of non-smoking women, the level of cotinine in 15 cases was 0 ng/ mg of creatinine, whereas in two cases, it amounted to 19.4 and 215.4 ng/mg of creatinine respectively. Among the persons, who were smoking, there were 4 cases, where the biomarker's level was 0 ng/mg of creatinine, and in 10 cases, the mean concentration of cotinine was 169.1 +/- 121.8 ng/mg of creatinine. The measurement of the content of tobacco-specific N-nitrosamines (NNAL- metabolite of NNK) in the urine of pregnant woman was carried out by means of the liquid chromatography/tandem mass spectrometry (LC/MS/MS). The analysis of obtained results showed that the mean concentration of NNAL in urine of smoking women was 59.2 +/- 40.2 pg/ ml. In the case of two patients, who declared to be non-smokers, and in the case of whom, the presence of cotinine was detected (19.4 and 215.4 ng/mg of and 88.4 pg/ml. The presence of 4-(metylnitrosamino)-1-(3-pyridyl)-1-butanol in the mother's urine, speaks volumes for the possible risk of exposure of a foetus to the cancerogenic components of tobacco smoke. The applied LC/MS/ MS method of determination of NNAL in urine, which allows the quantity of several pg/ml of the smoker's urine to be determined, can be used to mark the biomarker of exposure to the tobacco-specific N-nitrosamines. The lack of correlation between cotinine and NNAL concentration in urine, and the number of smoked cigarettes, speaks volumes for the lapse of quite a long time from the moment of cigarette smoking to the moment of collection of the biological material for research and the possible incredible declaration as to the number of smoked cigarettes. Only a slight tendency for the increase in the concentration of NNAL as well as the increase in the cotinine level could be caused by the difference in pharmacokinetic parameters of marked metabolites at the moment of smoking cessation.

A 52-year-old woman with a history of depression and personality disorders, hypertension, coronary disease and asthma was admitted to the Department of Clinical Toxicology after taking 60 tablets of Staveran (immediate release verapamil), and 4 tablets of acetaminophen. One and a half hours after ingestion her condition was critical. She required endotracheal intubation and artificial respiration. Her heart rate was 75 beats per minute, (bpm) and her blood pressure dropped from 70/50 to 50/00 mmHg. Additionally, drowsiness and headache were observed. On admission, R-(+)- and S-(-)-verapamil serum concentrations were 2252 ng/ml and 810 ng/ ml, respectively. Monitoring of the verapamil serum concentration was carried out over 74 h. Terminal elimination half-lives were 18.7 (21.3) and 17.0 (18.5) hours, respectively, for R-(+)- and S-(-)-verapamil. Monitoring of verapamil enantiomers concentrations in serum indicated a higher concentration of the less active form and slightly faster elimination of the more active enantiomer. The data-support a stereoselective difference between first pass clearance and later systemic clearance of verapamil, when taken in overdose.

An essential problem related to tobacco smoking is exposure of children in the foetal period and early childhood to toxic compounds. The aim of this paper was to assess the exposure of pregnant women and their newborns to polycyclic aromatic hydrocarbons as a consequence of tobacco smoking. The exposure to tobacco smoke was determined through surveys and cotinine measurement in the urine of pregnant women and newborns, and the exposure to polycyclic aromatic hydrocarbons has been determined by measure of 1-hydroxypyrene in the same biological material. The cotinine concentration in the urine of smoking women and their newborns was respectively 416.0 +/- 319.9 ng/mg of creatinine and 46.5 +/- 37.2 ng/mg of creatinine. In case of non-smoking as well as non-exposed patients and their newborns, the concentration of cotinine was 0. The correlation between the concentration of cotinine in the urine of smoking women and their newborns was shown. The mean concentration of 1-hydroxypyrene in the urine of smoking patients was 0.65 +/- 0.45 ng/mg of creatinine, whereas in the urine of newborns, it was 0.46 +/- 0.41 ng/mg of creatinine. The concentration of 1-hydroxypyrene in the urine of smokers was increased together with the increase of cotinine, and the correlation factor was 0.5128. Such dependence was not indicated for concentrations of these compounds in the urine of newborns of these women. Within the group of non-smoking women, the concentration of 1-hydroxypyene urine of women was 0.25 +/- 0.29 ng/mg of creatinine, whereas among children 0.20 +/- 0.23 ng/mg of creatinine. In both examined group (smoking and non-smoking women) there is a dependence between the concentration of 1-hydroxypyrene in the urine of women and their newborns. The research concerning the assessment of exposure of pregnant women and their newborns to polycyclic aromatic hydrocarbons was conducted, and at the same time it was proven, that the placenta does not constitute a barrier for these compounds, which may freely get into the fetus. Probably for the first time a relatively large group of patients took part in this research. The directly proportional dependence between the concentrations of 1-HP in a mother and a newborn and significantly lower concentrations of this biomarker among the persons who are not exposed to tobacco smoke, indicate that the pro-health behaviours of the future mother (no tobacco smoking) significantly lowers the exposure of foetus to the carcinogenic compounds.

The new method of treatment of addiction to nicotine "Reduce to Stop" constitutes new possibilities of using the Nicotine Replacement Therapy (NRT). This type of therapy consisting in a significant restriction of the number of cigarettes smoked per day with a simultaneous taking of nicotine preparations constitutes a chance of giving up a habit for smokers who want to quit smoking, but cannot do it or are not ready for it. The clinical research confirmed the effectiveness of this method not only in restricting smoking, but also in increasing the motivation to stop smoking or even total giving up of the habit.

Buprenorphine is a strong narcotic analgesic. It is also used in the substitution therapy for opium alkaloid addicts. The aim of this paper was to develop and validate a highly sensitive high-performance liquid chromatography-electrospray ionization-mass spectrometry method for simultaneous determination of buprenorphine and norbuprenorphine in human serum. The developed methodology was then applied to real clinical cases in a clinical toxicology setting. Extraction of analytes has been done using solid-phase extraction. Chromatographic separation was achieved on a LiChroCART column with a Purospher RP-18e cartridge, and for detection an LCQ mass spectrometer with an ion trap analyzer was used. Quantitation of buprenorphine and norbuprenorphine was performed in a single ion monitoring mode (m/z 468 buprenorphine, m/z 414 for norbuprenorphine) in order to increase the sensitivity of the method. The standard curves for both compounds were linear over the range of 0.2-10 ng/mL (r2 > 0.995). The quantitation limit was 0.2 ng/mL for both analytes. The method was used for quantitation of both buprenorphine and norbuprenorphine in the serum of 15 patients undergoing the buprenorphine substitution therapy. Serum concentrations ranged between 0.36 and 4.60 ng/mL for buprenorphine and 0.21 and 2.50 ng/mL for norbuprenorphine, with buprenorphine single dosages from 0.8 to 6.0 mg.

The aim of our study was an analysis of cotynine, the main nicotine metabolite in the urine among hyperthyroid patients. The study group included 39 females and 4 males. The mean age was 35.59+/-14.22 yrs. (range: 18-73 yrs.; median: 32 yrs) among hyperthyroid patients suffering from: Graves-Basedow disease (GB), Graves' Ophtalmopathy (GO) and toxic nodular goiter (TNG). To evaluate the nicotine smoking intensity and ETS Environmental Tobacco Smoke, the urine analysis of cotynine level were performed. According to the statistical analysis using the Mann-Whitney test, the statistically significant difference between the level of cotynine among smokers suffering from GO and Graves-Basedow disease was revealed (p = 0.03). Similar results were obtained among the GO and TNG (p=0.02) using t-Student test with Welsch correction. To compare, there was no stastistically significant difference between the GB and TNG series (p=0.4). In the group of smoking patients with GO we found out incresed level of urine cotinine than in smoking patients with GB and TNG. We didn't found differences between GB and TNG in depends on an urine analysis of cotynine level.

The aim of the study was to evaluate the exposure of smoking pregnant women (total number 52) to polycyclic aromatic hydrocarbons (PAH) on the base of determination of 1-hydroxypyrene in urine. Standardised survey questionnaire and determination of cotinine in urine estimated the smoking habit. In the case of smoking women the mean concentration of cotinine was 362+/-320 ng/mg creatinine, passive smokers had cotinine concentration 32+/-6 ng/mg creatinine and non smokers below 5 ng/mg creatinine. In the urine of pregnant women, 1-hydroxypyrene a biomarker of PAH exposure was measured. The urine of smokers contained 0.17+/-0.18 micromol/mol creatinine, passive smokers 0.11+/-0.20 pmol/mol creatinine and nonsmokers 0.10+/-0.12 pmol/mol creatinine. The obtained results confirmed the higher risk of exposure to PAH in group of smoking pregnant women, however cigarette smoke are not only one source of these cancerogenic compounds.

Teachers are an important part of anti-tobacco education. The aim of this study was evaluation of the level of tobacco smoking among teachers as well as to check their knowledge on tobacco toxicity. The study group consisted of 745 teachers from whom 671 participated in the study. We found that 32% teachers were smokers and it was a higher level than average for Polish population. Two thirds of responders were smoking from 6 to 20 cigarettes per day. 35% of teachers pointed tobacco smoke tar as risk factor of tobacco-related diseases (e.g. lung cancer). Similar percentage of responders pointed on the correlation between tobacco smoking and osteoporosis. As a conclusion of this study we would like to stress that the knowledge on tobacco-related topics among teachers is insufficient for a proper anti-tobacco education. In the future a repeated courses for teachers on such issues should be prepared.

Tobacco smoking is one of the principal causes of morbidity and mortality in the worldwide. By the year 2030, more than four million people per year worldwide will die of tobacco-related cause. No other consumer product is as dangerous as many people. Tobacco causes more deaths than any other dependence-producing substances, e.g. poor diet, alcohol, bacterial infections, poisoning, firearms, and illicit drugs. The morbidity and the mortality associated with tobacco use is caused by several toxic substances (e.g. nicotine, polynuclear aromatic hydrocarbons, aza-arenes, N-nitrosamines, aromatic amines, acrylonitrile, crotonaldehyde, vinyl chloride, formaldehyde, benzene, inorganic compounds). Tobacco smoking is a major independent risk factor for chronic obstructive pulmonary diseases (COPD), cancer (lung, larynx, pharynx, oesophagus, pancreas, kidney, urinary bladder, nasal cavity, uterine cervix), coronary heart disease (CHD) and reproduction. In 2004 42% of Polish man and 23% Polish women smoked. This publication presents a program that has been designed to educate medical students (fourth or fifth year) about tobacco in University of Medical Sciences. There are two parts in total six hours education. Part I is concerned with the epidemiology of smoking, the toxicology of tobacco smoke, the health effects of tobacco use, the process of smoking cessation, the treatment for smokers, and smoking prevention. Part II (workshops) deals with teaching medical students how to motivate patients to stop smoking. The second part consist of: identifying the smoker, taking a smoking history, evaluation of the level of dependence and assessing the smoker's readiness to stop smoking, motivating smokers to change, and preventing relapse. Both parts (theory and practical sessions), are scheduled to take three hours each.

One possible mechanism of lowering of the birth weight by tobacco smoke is disturbance in zinc transfer trough placenta caused by accumulation of cadmium in placenta. The aim of the study was determination of cadmium and zinc in placenta of smoking women and correlation its with cotinine concentration and birth weight The study shown that concentration of cotinine in urine of smoking woman was 859+/-1234 ng/mg creatinine. Cadmium and zinc concentrations in smokers were higher (Cd 0.095+/-0.041 microg/g; Zn 46.7+/-8.3307 microg! g) than in non smokers (Cd 0.067 +/-0.022 microg/g; Zn 41.0+/-5.54 microg/g). Concentration of cadmium in placenta shown week correlation with concentration of cotinine in urine. The birth weight of newborn of smoking women (2935.7+/-836.83 g) was statistically lower than non smokers (3288.9 +/-744.47 g), however it was not correlated with placenta cadmium and zinc concentration. The high variability of the ratio of zinc to cadmium concentration caused that was not statistical differences between studied groups. The performed research shown the influence of cigarette smoking of birth weight and cadmium concentration in placenta, however did not proved the hypotheses that accumulation of cadmium and zinc in placenta influence on birth weight.

The aim in this survey was analysis of contribution of exposure to tobacco smoke and selected socioeconomic factors in occurrence of low birth weight. The research was done on the group of 1528 pregnant women. Smoking habit was declared by 18.2% of women and passive exposure to tobacco smoke was stated by 31% of respondents. Significant association between active and passive smoking and socioeconomic status of respondents was observed. Cigarette smoking during pregnancy was the main cause of lower birth weight of newborns. The newborns of actively smoking mothers were lighter of about 332 g according to those ones of mothers who did not smoke and were not exposed to passive smoking, and were lighter than newborns of mothers who were not exposed to passive smoking of about 342 g.

Exposure to tobacco smoke impairs the antioxidant defense mechanisms. In female Wistar rats fed on regular rodent chow and supplemented with a flavonoids rutin, Trolox Equivalent Antioxidant Capacity (TEAC) was measured as an ABTS-radical cation reduction power in plasma, lungs, liver, brain and kidneys. Exposure to smoke reduced the TEAC values in the liver, brain and kidneys and enhanced antioxidant potential in lungs in comparison to control animals. In plasma no change of TEAC value was observed. Supplementation with rutin increased antioxidant status of plasma, but TEAC was reduced in kidneys, brain and liver of smoke-exposed animals when compared to the matched controls. In lung no change in TEAC was found. The results suggest a complex pattern of influence of tobacco smoke on blood and tissue antioxidant mechanisms. The enrichment of diet with non-nutrient antioxidant rutin did not result in direct improvement of tissue TEAC with the exception of blood plasma.

Tobacco smoke contain few thousands of chemical compounds, among them heavy metals. From toxicological point of view most important are lead, cadmium and radioactive polonium 210. The aim of the study was determination of cadmium in urine of tobacco smoking pregnant woman and checking if there is a correlation between the concentration of cadmium and cotinine, the most frequently used tobacco smoke biomarker. The study showed that concentration of cotinine in urine of smoking women was 702.5 +/- 1131.4 ng/mg creatinine and ranged from 50 to more than 6000 ng/mg creatinine. Cadmium concentration in smokers was 1.6 +/- 2.6 ng/ml and ranged from 0 to 11.5 ng/ml. In urine of woman who do not smoke and are not exposure to ETS was 1.1 +/- 2.2 ng/ml in the range 0-2.5 ng/ml and was not statistically different from concentration of cadmium in urine of smoking pregnant woman. In any one non-smoking woman, concentration of cadmium was not higher than 5 ng/ml, but in 11.8% of smoking women this level was exceeded. Calculations showed a weak correlation between concentration of cadmium and cotinine in urine of smoking pregnant women.

Activities of two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined in plasma of rats exposed to tobacco smoke (500, 1000 and 1500 mg CO/m3 air in 5 days) and to 1000 mg CO/m3 in 1, 2 and 3 weeks. When compared to controls, the SOD activity was decreased in the exposed animals, the lowest smoke dose gave the most pronounced effect and the highest dose revealed the least diminution. GPx activity was statistically higher in the rats inhaled with the highest smoke dose. Time of exposure did not effect GPx but SOD raised in correlation to week number, although it did not reach control values over the experiment period. The observed alterations in plasma probably mirror the organ adaptation to oxidative stress in animals exposed to tobacco smoke.

According epidemiological study tobacco smoking is popular addiction around the world. It was estimated, that one third of world population smoking tobacco. The statistical data from 2002 show that in Poland 42% of men and 22% of women smoke tobacco on a daily basis. As many as 60% of non-smokers are exposed to environmental tobacco smoke (ETS). The aim of the study was verification the answer on a standardised survey questionnaire (related to tobacco smoking) by laboratory method--determination of cotinine in urine. In the study participated 244 delivering women. In the tested group 23.8% of surveyed declared smoking during their pregnancy and around 28% of non-smoking women were exposed to passive inhalation of tobacco smoke. More than 15% of women, which declared non smoking has concentration of cotinine higher than 50 ng/mg creatinine (mean 227.3 ng/mg creatinine) what indicated active smoking of cigarettes. From these results we can conclude that as much as 35.6% of women smoking tobacco during pregnancy and is higher than suggested the questionnaire examination.

Nicotine replacement therapy (NRT) play a major role in pharmacotherapy of nicotine dependence. Currently various nicotine formulations are sold as over-the-counter (OTC) products in several European countries. The effectiveness and safety of nicotine formulation was proved in many countries in population studies. The most often used NRT products are nicotine chewing gum and Nicotine transdermal patch.

Among other toxic compounds, tobacco smoke contains also heavy metals, for example lead. Lead can cross the placenta barrier and have negative influences on fetus development. In the study compared urine lead concentration of pregnancy women exposed to tobacco smoke (active smokers and exposed to environmental tobacco smoke--ETS) with unexposed. There was find that mean urine lead concentrations in groups of pregnant women exposed and unexposed to tobacco smoke was no different (F2,189=0.2 p>0.8). However it was found that in urine of women exposed to tobacco smoke the concentration of lead increase with increase the concentration of cotinine (r2=0.14, t106=4.2, p<<0.0001).

The subject of the research was the analysis of frequency and type of psychoactive substances used, basing on the determinations the blood and/or urine samples, performed in the toxicological laboratory of the Department of Clinical and Industrial Toxicology Jagiellonian University in Kraków in the period from December 2001 to November 2003. From 17,649 performed determinations--45.5% were positive. 50% of the positive determinations were psychoactive substances. The most often psychoactive substance determined was ethyl alcohol (52.86%), next benzodiazepines (17.41%), amphetamines (10.54%), opiates (8.05%), THC (6.87%), barbiturates (3.74%), and occasionally atropine and cocaine. There was observed a variety of mixed, simultaneously taking psychoactive substances, especially ethyl alcohol, opiates, amphetamine derivatives and cannabinoids. The analysis of the occurrence of psychoactive substances in biological samples from patients treated in different hospital departments, others hospitals and ordered by private persons also was performed. In the last two years 369 private patients ordered psychoactive substances determinations and 78 of them were positive.

Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and this is the main way of alcohol oxidizing in social drinkers. Microsomal Ethanol Oxidizing System (MEOS) is induced in ethanol addicted individuals and plays the main role in ethanol oxidation in this group. The aldehyde dehydrogenase (AIDH), enzyme oxidizing acetaldehyde to acetic acid, activity is not induced and does not get changed. This may lead to acetaldehyde cumulation in alcoholics. The aim of the study was to define the usefulness of acetaldehyde concentration measurement in the blood as the marker of alcohol addiction. 53 alcohol addicted and acutely poisoned patients (males) participated in the study. The control group was social drinkers, 43 males, accidentally poisoned with ethanol. Alcohol addiction was diagnosed according to ICD-10 criteria. Ethanol and acetaldehyde measurements were carry out on admission. The ethanol concentration in blood was measured by enzymatic method (ADH) and acetaldehyde concentration using headspace gas chromatography. Because of differences of ethanol concentrations in two examined groups (alcoholics and social drinkers) the normalization of acetaldehyde results was performed dividing acetaldehyde concentration by ethanol concentration. The results indicated higher blood acetaldehyde and ethanol concentrations in alcoholic individuals acutely poisoned with ethanol in comparison to acutely poisoned social drinkers. The acetaldehyde/ethanol ratio, used in the study, is higher in alcoholics as well and the difference is statistically significant. These results suggest the usefulness of acetaldehyde concentration measurement as a marker of ethanol addiction.

Total antioxidant status was measured as the reduction of the ABTS radical cation as well as the activities of SOD and GPx in female rats exposed and non-exposed to the cigarette smoke, pregnant and non-pregnant. The assessment was done in lungs, plasma, kidneys, liver and placenta of Wistar rats exposed to the cigarette smoke (1500 mg CO/m3 air) for 21 days. Total antioxidant status was significantly elevated in lungs and plasma of smoke-exposed animals, pregnant and non-pregnant, when compared to the matched controls. In other examined tissues antioxidant capacity was diminished in all tested groups of animals. Activities of SOD and GPx were markedly decreased in tissues of all examined animals. Exposition to the cigarette smoke, despite some changes due to the adaptation to stress, diminishes the antioxidant capacities of the body and in the pregnant animals it may effect the pregnancy outcome.

The aim of this study was to evaluate the exposure of pregnant women to tobacco smoke on the basis of a standardised survey questionnaire, and determination of cotinine in urine. In the study participated 133 women delivering, checked in at the Obstetric Department of Independent Public Health Care Unit in Srem in 2003. The all women fill in the questionnaire forms referring smoking and exposure to ETS (Environmental Tobacco Smoke). In the tested group 22.6% were smoking during pregnancy. Only 5 pregnant women quit smoking, however around 60% of smokers reduced the number of cigarettes. Near 56% of women were exposed to ETS, mainly during social events. In case of women, who declared smoking the mean concentration of cotinine was 2164 ng/mg of creatinine. Passive smokers had cotinine concentration between 10 and 50 ng/mg of creatinine Cotinine may be used to validate tobacco smoke exposure assessment from surveys.

The activity of zinc administered intraperitoneally, acutely (in single dose), sub-chronically (in triple doses) or chronically (once daily for 14 days) were assessed in the forced swim test (FST) and olfactory bulbectomy (OB) model of depression in rats. Previously, we have demonstrated that acute administration of zinc sulfate is active in FST in rats and mice. In the present study, zinc hydroaspartate in a dose of 65 mg/kg (11.5 mgZn/kg), all: acute, sub-chronic and chronic administration, reduced the immobility time in the FST in rats. Removal of olfactory bulbs (OB surgery) in rats is associated with variety of behavioral abnormalities such as deficit in a step-down passive avoidance or hyperactivity in the "open field" test. Both acute and chronic administration of zinc hydroaspartate reduced the number of trials needed to the learning passive avoidance and reduced the OB-induced hyperactivity in rats. At the time schedule following zinc hydroaspartate administration, when behavioral experiments were performed, the serum zinc concentrations were significantly higher than control-physiological values. These results confirm activity of zinc in the FST, show its antidepressant-like activity in the OB rat model of depression, demonstrate the lack of tolerance to these effects and suggest relationship of these antidepressant-like effects with the rise in serum zinc. These animal data further suggest antidepressant activity of zinc in human depression.

Zinc is involved in both psychopathology and treatment of depression. Since a considerable percentage of suicide victims had suffered from depression, we hypothesized that alteration in zinc homeostasis might occur in their brain tissue. We now report that zinc content is not altered in the hippocampal or cortical tissue of suicide victims (n = 10) compared to age-matched controls (n = 10). However, there is a statistically significant 26% decrease in the potency (increase in the IC(50) value) of zinc to inhibit [(3)H]MK-801 binding to NMDA receptors in the hippocampal but not cortical tissue of suicide subjects. The data represent the first demonstration that the alteration in zinc interaction with NMDA receptors may be involved in psychopathology underlying suicidal attempts.

The study was done in 57 psychoactive drug addicts (18 females and 39 males) who entered a methadone maintenance program in Szczecin. The age of participants ranged from 21 to 49 years (mean 32.14 years) and the mean duration of drug abuse as determined during history-taking was 11.6 years. Some of the patients became addicted at the age of just 11 years. The objectives of this work were: a) to apply segmental analysis of hair for studying psychoactive agents and their derivatives in drug abusers during the acute intoxication phase and maintenance therapy; b) to determine if narcotics found in hair matched with findings during history-taking; c) to check the relevance of toxicological tests for psychoactive drug content in hair for monitoring abstinence in maintenance programs. The material consisted of hair sampled from 57 patients who were visited the Outpatient Department for Drug Abusers of the Regional Mental Care Center in Szczecin (Poland). Opioids (morphine, codeine, 6-mono-acetyl-morphine, methadone) were determined using gas chromatography/mass spectrometry (GC/MS-ITD) and a Varian 3400 gas chromatography (USA) coupled to a mass spectrometer (Magnum ionic trapping system, Finnigan Mat, USA). Amphetamines (EP, MK, MA, AMP, MDA, MDMA, MDEA) were analyzed with a liquid chromatography/mass spectrometry (LC/MS) system (LC/MS HP-1100, Hewlett-Packard, USA), equipped with an atmospheric pressure chemical ionization (APCI) chamber and dedicated software. Statistical analysis of the results was done. The following conclusions were drawn: toxicological examination of narcotic content in hair is a useful method for studying the history of drug addiction during the period of time equivalent, to the length of hair. Psychoactive substances detected in hair were in most cases consistent with the history of drug abuse. Analysis of psychoactive substances in hair may be applied for identification of addicting drugs and for abstinence control in therapeutic and rehabilitation programs.

Basing on toxicological examination performed between December 1, 2001 and November 6, 2002 the analysis of cardiotoxic agents was carried out. As much as 69.7% of 2523 positive results was related to cardiotoxic agents. Ethanol (57.4%) followed by anticholinergic drugs (15.7%), amphetamine (11.6%) and carbon monoxide (8.9%) were most frequently determined cardiotoxic agents. Relatively small number of cardiovascular medication drugs (0.3%) was stated in biological samples. The cardiotoxic agents were detected mostly in men (68.8%), even after ethanol was excluded from the analysis (54.8%).

The study attempts to evaluate whether it is possible to determine time and level of exposure of rats to tobacco smoke based on nicotine and cotinine content in urine. The animals were exposed to tobacco smoke by inhalation in a specially designed experimental chambers. The exposure to three different tobacco smoke levels (500, 1000 and 1500 mg CO/m3 of air) lasted 6 h per day, for one, three and five days. Nicotine and cotinine concentrations were measured in daily urine using high performance liquid chromatography procedure developed by the authors. It has been shown that cotinine but not nicotine can be used as a biomarker of time and extent of exposure to tobacco smoke.

A study was carried out on 92 patients (58 males and 34 females) aged 42-76 treated for malignant neoplasm of the gastrointestinal tract (54 patients with colorectal carcinoma, 38 with gastric carcinoma). In all patients, the zinc serum concentration was measured and the results obtained were referred to some epidemiological-clinical factors (sex, age, primary cause of cancer, the stage of clinical progression, and histological type). The results showed that the most pronounced hypozincemia occurred in male patients with mucous membrane carcinoma of the stomach.

The presence of volatile compounds, such as acetone, acetaldehyde, methanol, ethanol, isopropanol, and n-propanol, in the blood of 169 acutely poisoned alcoholics was determined. The clinical diagnosis of addiction was made on the basis of a patient interview as well as physical, psychological, and psychiatric examination. At the time of the patients' admission to the clinic, the mean concentration of ethanol in blood was 3.14 +/- 1.10 g/l and its elimination rate in the studied group was 0.27 +/- 0.08 g/kg/hr, an elimination rate significantly higher (P <.001) than that of social drinkers, which averages to 0.014 +/- 0.04 g/kg/h. The presence of other volatile compounds in the blood of alcohol-addicted patients is common. The calculated elimination rate constant of methanol was about 0.2 h(-1). This rate seems to indicate that, in heavy drinkers, the elimination of methanol may be relatively fast even if the ethanol concentration is above 1 g/l. The elimination of other volatile compounds can be accelerated by large doses of ethanol, although it is not correlated with actual blood ethanol level. Moreover, in most of the blood samples with a methanol concentration below 10 mg/l, the measured concentration of acetone was below 7 mg/l and that of isopropanol was below 2 mg/l.

The analysis included 46 patients (27 men and 19 women), aged 41 to 76 years, who required intensive medical care because of a grave clinical state. In all af them, as in a group of patients treated because of illnesses identical to those of the basic group but not requiring intensive medical care (CG), as well as in a reference group (RG)--blood donors, the determinations were conducted of the magnesium concentration in the serum with the flame atomic absorptive spectrometry method. It was confirmed that in the patients in grave clinical state the average concentration in the serum of that element was statistically significantly lower that in the other groups (CG and RG). The average magnesium concentration also differs statistically really between the CG and RG. A critical value was also determined of the magnesium concentration in the serum raising 5.78 micrograms/ml, which may be the prognosis of the metabolic disturbances leading to a grave clinical state.

The analysis included 80 patients (48 men and 32 women) aged 65 to 87 years, treated because of cancer of the stomach (34 causes) or of the large bowel (46 causes). In all the patients as well as in a control group made up of persons who were treated because of non-neoplastic diseases of the gastrointestinal tract the determinations were conducted of selected coagulological parameters: fibrinogen and D-dimer concentration, antithrombin III (AT III) activity, kaolin-cephalin index (APTT), prothrombin (PT), thrombin time (TT) and number of thrombocytes in the blood. The analysis of the results obtained showed that hemostasis disturbances of a chronic DIC character occur in 82.5% of persons of an advanced age ill with a cancer of the stomach or of the large bowel.

The study was carried out on 48 patients (26 male and 22 female), aged 52-76 diagnosed as having cancer metastases to the liver. The serum level of magnesium in the studied group and also in two other groups (the first consisting of 48 blood donors and the second of 50 patients suffering from cancer of a non-disseminated nature) was measured by the flame atomic absorption spectrophotometric method. The results of the study showed that cancer metastases to the liver significantly decrease the mean level of magnesium in serum compared to the other two groups. It was shown that a magnesium level below 12.76 micrograms/ml in cancer patients increased the risk of cancer metastases to the liver.