Resveratrol Relaxes Human Gastric Smooth Muscles Through High Conductance Calcium-Activated Potassium Channel in a Nitric Oxide-independent Manner.

Resveratrol, as a polyphenolic compound that can be isolated from plants, and also a component of red wine has broad beneficial pharmacological properties. The aim was to investigate the role of nitric oxide and potassium channels in resveratrol-induced relaxation of human gastric smooth muscle. Gastric tissues were obtained from patients who underwent sleeve gastrectomy for severe obesity (n = 10 aged 21-48; BMI 48.21 ± 1.14). The mechanical activity from the muscle strips was detected under isometric conditions as the response to increasing concentrations of resveratrol before and after different pharmacological treatments. Resveratrol caused an observable, dose-dependent gastric muscle relaxation. The maximal response caused by the highest concentration of resveratrol was 83.49 ± 2.85% (p < 0.0001) of the control. Preincubation with L-NNA, L-NAME, or ODQ did not prevent the resveratrol-induced relaxation. Apamin, glibenclamide, 4AP or tamoxifen, did not inhibit the relaxing effect of resveratrol, as well. In turn, blocking BKCa by TEA, iberiotoxin, or charybdotoxin resulted in inhibition of resveratrol-induced relaxation (91.08 ± 2.07, p < 0.05; 95.60 ± 1.52, p < 0.01 and 89.58 ± 1.98, p < 0.05, respectively). This study provides the first observation that the relaxant effects of resveratrol in human gastric muscle strips occur directly through BKCa channels and independently of nitric oxide signaling pathways. Furthermore, there is considerable potential for further extensive clinical studies with resveratrol as an effective new drug or health supplement to treat gastrointestinal dyspepsia and other gastric hypermotility disorders.

Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies.

OBJECTIVE: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. DESIGN: This was a controlled and prospective ex vivo study. SETTING: The work was conducted as a collaboration between 4 academic departments. MATERIALS AND METHODS: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. RESULTS: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). LIMITATIONS: These results require now to be placed into a firm clinical context. CONCLUSIONS: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Quercetin relaxes human gastric smooth muscles directly through ATP-sensitive potassium channels and not depending on the nitric oxide pathway.

BACKGROUND: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels. METHODS: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. KEY RESULTS: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10-7  mol/L and maximal at 10-4  mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control. Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10-5  mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10-6  mol/L). Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations. CONCLUSIONS & INFERENCES: In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K+ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.

Intraoperative Peritoneal Interleukin-6 Concentration Changes in Relation to the High-Mobility Group Protein B1 and Heat Shock Protein 70 Levels in Children Undergoing Cholecystectomy.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin.

BACKGROUND: Uterotonic mediators: endothelin-1 (ET-1), arginine vasopressin (AVP), and nitric oxide (NO) play important roles in the regulation of uterine contractility. We hypothesize that NO affects both ET-1 or AVP. Therefore, this study investigated the involvement of extended exogenous NO release in the regulation of responses of the human non-pregnant myometrium to ET-1 and AVP. METHODS: Specimens were obtained from 10 premenopausal women, undergoing hysterectomy for benign gynecological disorders. Responses of the myometrial strips to ET-1 or AVP in the absence and presence of an exogenous NO donor (diethylenetriamine; DETA/NO; 10-4 mol/L) were recorded under isometric conditions. To inhibit endogenous NO, a competitive inhibitor of NO synthase, L-NG-nitroarginine (L-NNA) was added to the organ bath. RESULTS: ET-1 enhanced the spontaneous contractile activity of the myometrium more powerfully (p < 0.01) than AVP. Preincubation with exogenous NO weakened ET-1- or AVP-induced increases in this contractile activity (p < 0.05). However, unexpected results were obtained after preincubation with L-NNA and with DETA/NO then added. Both ET-1 and AVP induced augmented contractile effects in almost all concentrations compared with the responses to these peptides alone or after NOS synthase inhibition (both p < 0.01). CONCLUSIONS: This study demonstrated for the first time that extended incubation with a NO donor influences the uterine muscle response evoked by ET-1 and AVP. Both endogenous and exogenous NO is involved in the control of the uterine responses to ET-1 or AVP of non-pregnant myometrium. Furthermore, both peptides stimulate increased uterine contractility when the local imbalance between the constrictive and relaxing mediators takes place.

The effect of the release of exogenous nitric oxide on the responses of the pregnant human myometrium to oxytocin.

OBJECTIVE: Introduction: Currently there is insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labor. An understanding of the role that nitric oxide plays in the management of threatened preterm labor may lead to more effective treatment and prevention. The aim of our study was to examine the involvement of exogenous nitric oxide release in regulating responses of the human pregnant myometrium to oxytocin. PATIENTS AND METHODS: Material and methods: Biopsies of human myometrial tissue during pregnancy were obtained from 8 pregnant women, aged 21-35 years. The responses of the specimens to oxytocin in the absence and presence of a DETA/NO were recorded under isometric conditions. Preincubation with exogenous nitric oxide significantly (p<0.001) attenuated the contractile response of the uterine strips to oxytocin in concentrations higher than 10-8 mol/L. RESULTS: Results: The inhibition of nitric oxide synthesis alone or in combination with DETA/NO incubation did not significantly change the oxytocin contractile effect in the concentration-response curve. Moreover, there was no significant variation in the mean value for log EC50 for oxytocin between the group with oxytocin alone and other groups. CONCLUSION: Conclusions: We present evidence in support of the hypothesis that continuous nitric oxide supply to the human pregnant myometrium environment attenuates its response to oxytocin but only when endogenous production of nitric oxide is not impaired.

The sources of calcium for noradrenaline-induced contraction in the human thoracic internal artery.

The aim of the present study was to examine the contribution of intracellular and extracellular calcium sources in contraction caused by noradrenaline (NA) of the human internal thoracic artery (ITA) in vitro. Distal segments of ITA were obtained from 20 patients (aged 38-73, at the time of routine coronary artery surgical revascularization (CABG)). Contractile responses to 10-6 mol/L NA in the physiological salt solution and in Ca2+-free solution without and after incubation with 10-6 mol/L thapsigargin (TSG) were recorded under isometric conditions. Responses of ITA rings to 1 µM NA without incubation with TSG accounted (% of reaction to 80 mM KCl) 224.70 ± 14.06% in PSS solution, 141.30 ± 8.66% in Ca2+-free solution, and 80.03 ± 1.71% after PSS restoration and were statistically significantly different (p < 0.0001, one-way ANOVA). Responses of ITA rings to 1 µM NA with 1 µM TSG accounted (% of reaction to 80 mM KCl) 114.50 ± 2.79% in Ca2+-free solution and 36.70 ± 2.38% after PSS restoration. Responses in Ca2+-free solution and after PSS restoration without and with TSG were statistically significantly different (p = 0.0257 and p < 0.0001, respectively-t test). ITA contraction is caused by calcium derived not only from the SR and the extracellular matrix. The delivery of calcium to the space surrounding tissue does not immediately deliver calcium to the myofilaments.

Altered uterine contractility in response to ß-adrenoceptor agonists in ovarian cancer.

We aimed to prospectively examine ß-adrenoceptor-mediated uterine contractility in women suffering from gynecological malignancies. Myometrial specimens were obtained from non-pregnant women undergoing hysterectomy for benign gynecological disorders, and ovarian, endometrial, synchronous ovarian-endometrial, and cervical cancer. Contractions of myometrial strips in an organ bath before and after cumulative dosages of ß2- and ß3-adrenoceptor agonists with preincubation of propranolol, SR 59230A, and butoxamine were studied. All agonists induced a dose-dependent attenuation for uterine contractility in endometrial or cervical cancer, similar to that observed in the reference group. Contradictory effects were observed for ovarian cancer alone or in combination with endometrial cancer. CL 316243 or ritodrine abolished the relaxation, whereas BRL 37344 increased the uterine contractility in ovarian cancer. Moreover, ß-adrenoceptor antagonists caused varied effects for ß2- or ß3-adrenoceptor agonists. Our experiments demonstrate that ovarian cancer, alone or as synchronous ovarian-endometrial cancer, substantially alters uterine contractility in response to ß-adrenoceptor agonists.

Levels of vitamin C In the blood plasma patients treated with coronary artery bypass grafting increases significantly after surgery.

One strong risk factor of coronary artery disease (CAD), which affects the levels of vitamin C in the blood is cigarette smoking. The supplementary effects of coronary artery bypass grafting (CABG) is smoking cessation by patients. Therefore, the aim of this study was to examine the level of vitamin C in the blood plasma one day before and one month after CABG. Human blood were collected from 20 patients (men); 1day before and 1 month after CABG. All patients were smoker and after CABG they declared their not smoking. The concentration of vitamin C in the blood plasma was assayed by FIA method with spectrophotometric detection. The mean value of the vitamin C concentration 1day before CABG was 12.36±2.84µmol/L (mean±SD), 1 month after CABG 40.07±10.95µmol/L (mean±SD). The average increase in the concentration of vitamin C was 3.27±0.73 times (mean±SD) and showed significant positive correlations (Pearson r=0.657, p=0.002). It should be consider incorporating the recommendations of preoperative smoking cessation for at least one month prior to CABG and/or additional supplementation. In addition it would be relevant to monitor the level of vitamin C in the patients' blood in the preoperative period.

Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated.

BACKGROUND: The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels. METHODS: Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection. RESULTS: AA concentration (mean±SD); men: 98,7±13,18µg/g tissue, women: 96,06±11,98µg/g tissue. Cadmium concentration(mean±SD); men: 309±103,71ng/g tissue, women: 348,5±255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144). CONCLUSIONS: Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.

Cu(II) complexation does not affect oxytocin action on pregnant human myometrium in vitro.

OBJECTIVE: Copper may influence the in vivo and in vitro uterine activity. Recent evidence shows that cupric ions can easily form complexes with oligopeptides like oxytocin (OXT). The high complex stability in vitro suggests a possibility of complex formation in vivo. STUDY DESIGN: In vitro isometric contractions were recorded in uterine tissues from pregnant women undergoing caesarean sections and the effect of OXT and the Cu-OXT complex on isolated human pregnant myometrium was investigated. RESULTS: In the concentration range from 10(-14) to 10(-6)M of OXT alone, pre-formed Cu-OXT complex, and OXT following sample preincubation with Cu(II) salt, nosignificant differences were observed for the following parameters of pregnant uterine smooth muscle contraction: the area under the curve, frequency and amplitude of contraction. CONCLUSION: The binding of Cu(2+) ions does not abolish the ability of OXT to interact with oxytocin receptors and stimulate myometrial contraction in vitro.

Potassium induced contraction of the internal thoracic artery in vitro is time related: the potential consequences in the analysis of the mechanism of the spasm after coronary artery bypass grafting and in the analysis of the results of in vitro studies.

The aim of the present study was to examine how, under in vitro conditions, the human left internal thoracic artery (LITA) reacts to contractile agonist:potassium chloride (KCL) as a function of time, as well as to examine whether a change in the LITA reactivity can correlate with the occurrence of the refractory vascular spasm (RVS). Distal segments of LITA obtained from 33 patients aged 38-73, at the time of routine coronary artery surgical revascularization (CABG). Contractile response to 80 mmol K(+) was recorded under isometric conditions. In 16 (48,5 %) LITA segments, contractile reaction to K(+) after experiments ranging 1-10 h were registered. No contractile response even after 10 h of incubation was observed in 17 (51.5 %) LITA segments. Between 120 and 300 min after the beginning of the experiment, the reaction was maximum and amounted up to 300 % control reaction, then decreased. First, with respect to in vitro research isolated by LITA rings, while analyzing the results of the research, one should take into consideration the possibility that during the research, the functional state of the tissues changes and in particular its sensitivity to depolarization of the cell membrane. Second, the change in the sensitivity to depolarization of the cell membrane of the smooth muscles' LITA might be the potential mechanism causing the occurrence of the postoperative spasm after the CABG treatment.

[Evaluation studies of "Pro-health Programme for 2013-2016" implemented in State Higher Vocational School in Suwalki]. / Badania ewaluacyjne "Programu Prozdrowotnego na lata 2013-2016" wdrozonego w Panstwowej Wyzszej Szkole Zawodowej w Suwalkach.

INTRODUCTION: Evaluation studies (evaluation) is an act of gathering, analyzing and assessing the data in order to supply knowledge necessary to take decisions about future actions. It is a process of systemic gathering of information on personnel, products as well as workings, characteristics and results of programmes. It is a systematized study, observation and interpretation of the data. The aim of the evaluation of Pro-health Programme implemented in State Higher Vocational School of Suwalki has been the assessment of students' attitudes and behaviours following the introduction of the programme. What we have been interested is whether the students got involved in the implementation of the programme and the manner in which activites conducted within the framework of the project have changed their lifestyle. These activities should be correlated with the students' participation in evaluation studies that make it possible to correct errors arising in the course of implementation of the pro-health programme and to diagnose problems as well as search for solutions adequately adjusted to the encountered ambiguities. MATERIAL AND THE METHODS: In the academic year 2013/2014 in prof. E. Szczepanik State Higher Vocational School of Suwalki an authorial survey reasearch on pro-health attitudes of students of selected medical fields of study. They were planned as long-standing activities (2013-2016) aimed at verification of students' pro-health attitudes in the researched higher education institute. As essential role of evaluation studies, forecasting long-term effects and intended or unintended outcomes that transcend the time and site of the implementation of the programme were the reasons for undertaking the studies described hereinbelow. RESULTS: Less than half of the researched students is of the opinion that the pro-health programme implemented in State Higher Vocational School fulfils its objectives. Moreover, an overwhelming majority of the respondents think that tasks implemented within the framework of the pro-health programme have had an influence on shaping their pro-health awareness. CONCLUSIONS: 1. Evaluation of pro-health awareness should lead to changes in pro-health attitudes of the surveyed population. 2. Both the experience gained during the health improving activities and the student evaluation questionnaire analysis should lead to strengthening the main motivating factors that promote health improving.

[Estimating the prevalence of tobacco addiction by a method of online survey among students from Lviv and Suwalki]. / Szacowanie rozpowszechnienia nalogu palenia tytoniu metoda ankiet online wsród studentów ze Lwowa i z Suwalk.

INTRODUCTION: Poland and Ukraine are countries with a common 535 km border as well as the same cultural roots. This is why we might determine that the young people from Ukraine and Poland would have the same behaviours. On the other hand, the Polish-Ukrainian border is the external border of the EU, and Polish' membership in the EU does change the model of behaviour. An interesting aspect of this joint research is that Poland is one of the EU countries that are exposed to the phenomenon of smuggling of tobacco products. It is determined by the location of the border with Russia, Belarus and Ukraine, from which most of the illegal cigarettes in EU are smuggled. Usually, these cigarettes are destined for the countries of Western Europe and Poland is only a transit country. Recently though, it is more and more becoming a country of destination for cigarette smuggling. Therefore, in times when Ukraine plans to sign an association agreement with the European Union, it is interesting to examine the pro-health attitudes that are most common among young people living on both sides of the border. This is even more interesting that the study concerns not only cultural, but also economical issues, because inappropriate behaviors from childhood and young adulthood may be the cause of many future diseases such as stroke or heart attack. AIM OF THE RESEARCH: Estimating the prevalence of tobacco addiction using web-based surveys LimeSurvey among virtual research teams of students from Lviv and Suwalki. MATERIAL AND METHOD: In the academic year 2012/2013 at the Medical University in Lviv and at the Higher State Vocational School in Suwalki a survey on the lifestyle of medical students of different majors was conducted with a special regard to smoking. RESULTS: Students from Lviv and Suwalki are characterized by the same moderate level of healthy lifestyle awareness and make the same mistakes concerning negative health effects. APPLICATION: Students of medical majors, despite higher-than-average knowledge on the correct healthy behaviors do not implement their knowledge to real life. It is necessary to pay more attention to this group of young people while carrying on health awareness programs as encouraging young people to lead a healthy lifestyle can significantly affect the reduction in the risk of lifestyle diseases.

Effect of nitric oxide on responses of the human uterine arteries to vasopressin.

Nitric oxide (NO) is known to be an important relaxant of contractile activity in various muscles including the human uterine arteries. It has been suggested that NO plays a role in modulation of vascular action of arginin vasopressin (AVP), a strong vasoconstrictor of the human uterine arteries. Therefore, the purposes of this study were to investigate an involvement of endogenous NO in regulation of responses of the human intrauterine arteries to AVP and examine the effect of exogenous NO on contractions of the human intrauterine arteries evoked by AVP. Pretreatment of the artery rings with L-NA, an inhibitor of NO synthase significantly increased the resting force and enhanced the artery responses to AVP. The opposite effect has been observed after administration of 10(-6) mol/L sodium nitroprusside (SNP). Pretreatment of the artery rings with 10(-7) M CTX, a blocker of Ca(2+)-sensitive potassium channels with large conductance, did not change significantly their responses to AVP. Glibenclamide (1.5.10(-6) mol/L), a blocker of ATP-dependent potassium channels and apamin (10(-8) M), a specific blocker of Ca(2+)-sensitive potassium channels with small conductance strongly enhanced the maximum responses of the artery rings to AVP. Pretreatment with CTX significantly decreased the relaxation induced by SNP while apamin attenuated the sensitivity to SNP resulted in rightward shift of the concentration-response curve to SNP. In conclusion, this study indicates that: NO plays a role in regulation of both the vascular tone of the human intramyometrial arteries and their response to AVP. Ca(2+)-sensitive K(+) channels with small and large conductance are involved in the SNP-induced relaxation of these arteries. The pathways of this relaxation cannot be sufficiently explained at this moment and need further investigation.

[The comparison of ascorbic acid concentration in smokers with diabetes mellitus type II scheduled for coronary artery bypass grafting (CABG) to ascorbic acid concentration during postoperative and convalescence period]. / Por6ównanie poziomów kwasu askorbowego u palaczy chorych na cukrzyce typu 2 oczekujacych na operacje pomostowania tetnic wiencowych (CABG) z poziomami kwasu askorbowego w okresie pooperacyjnym i rekonwalescencji.

Cardiovascular disease is the main cause of increased mortality in diabetes patients. Myocardial infraction and stroke is in 60% to 80% causes reason of death in patients with type 2 diabetes mellitus. The main risk factor of cardiovascular disease is hyper-glycemia, hyperinsulinaemia and hypertension. The other arteriosclerosis risk factors are for example smoking. We measure the concentration of ascorbic acid in smokers' diabetes patients with type 2 diabetes mellitus with stable coronary disease scheduled for coronary artery bypass grafting (CABG). Vitamin C is assumed to be a basic antioxidant although its role in pathological conditions is controversial. However, it seems that the complexity of the oxidant-antioxidant system makes the question of participation of ascorbic acid in pathogenesis of diseases still open. Determination of the role of ascorbic acid concentration in pathogenesis of diabetic angiopathy may be of significant importance in the their effective therapy.

[Determination of cadmium level in passive tobacco smokers schizophrenia patients]. / Badanie poziomów kadmu u biernych palaczy tytoniu chorujacych na schizofrenie.

Schizophrenia is a long-term illness which concerns 1.4% of human population. It has been known as periodical or continuous, emotional or social disorder and it could cause substantial mental disability often leading to suicidal behavior or various other life threatening situations. Schizophrenic patients can not be classified as a homogenous group. The differences are caused by various psychopathological symptoms, different course of illness and different reactions to neuroleptic drugs among patients. Often these differences as well as connections with patients characteristics and symptoms of illness suggest the common name to the illness as "schizophrenia group" which includes mental illness of various etiopatogenesis and different psychobiological basis. Schizophrenia patients belong to the group of highest level of dependency on nicotine. It has been found that dependency on nicotine in this group is 1.5-2 times higher than in general population. Modern pharmacology started in 1952 when chlorpromazine was given for the first time to the mentally ill patients in St. Anne hospital in Paris. This breakthrough allowed mentally ill patients keep on undertaking treatments outside the hospital. The possibility of getting significant improvement in treatment of incurable, until now, illness paved the way for changes in general opinion about mental illness, particularly schizophrenia. Derivate of phenothiazine have been the oldest and most frequently used psychotropic drugs in Poland. They belong to the most numerous group of heterocyclic organic compounds which contains an aromatic triple-ring complex with atoms of sulfur and nitrogen. Therapeutic monitoring of drugs started at the end of sixties. Necessity of individualization of drugs in order to keep effectiveness and safety on proper level was an immediate answer to differences in intensity of pharmacological reaction to the drugs dosages among patients. Therapeutic monitoring is a method which anticipates a certain model of treatment depending on the results of clinical and pharmacological medical research. Therapy monitored by concentration of drug (TDM) is a mean to conduct therapy simultaneously with measuring concentration of drug in biological fluid. The results of lab research directly influence the dosages of drug.

[Evaluation test of cadmium concentration influence on selected lipid metabolism parameters in smokers with stable coronary artery disease scheduled for coronary artery bypass grafting (CABG)]. / Próba oceny wplywu stezenia kadmu na wybrane parametry metabolizmu lipidów w krwi palaczy tytoniu ze stabilna choroba wiencowa zakwalifikowanych do zbiegu pomostowania tetnic wiencowych (CABG).

The influence of cadium from cigarette intoxication on selected lipid metabolism parameters in smokers with stable coronary artery disease scheduled for coronary artery bypass grafting (CABG) was studied. It has been shown that concentration of cadmium leads to an increase in the lipid peroxidation and changes in the lipid metabolism. In our study, there was a significant higher cadmium concentration in smokers with stable angina pectoris (20.90+/-0.18) compared to stable angina pectoris non-smokers (7.71 +/-0,45), p<0.0001. We have not found correlations between cadmium concentration in smokers and non-smokers with stable angina pectoris patients and total cholesterol, LDL, HDL, and triglicerydes concentrations. Total cholesterol, LDL, HDL and TG concentrations in smokers scheduled for CABG were respectively: 221.60+/-10.26 mg/dl; 148.40+/-8.71 mg/dl; 41.16+/-2.12 mg/dl, 159.10+/-14.49 mg/dl. All of these lipid parameters in stable angina pectoris smokers did not differ significantly from non-smokers.

The fractal box dimension on human eyeball movement--objective, biological marker of schizophrenia?

The authors developed a method of measuring the fractal box dimension of the human eyeball movement. We found a fractal property in schizophrenic subjects (n = 20) and normal controls (n = 20). The value of the fractal box dimension for schizophrenic patients differs from the results obtained in the control group.

Influence of low molecular weight heparin preparations on human internal thoracic artery contraction.

OBJECTIVE: Low molecular weight heparins (LMWHs) offer practical and potential pharmacological advantages over unfractionated heparin in multiple applications but have not been studied as vasoactive agents. The purpose of this study was to investigate the effects of two commercial preparations of LMWHs, enoxaparin sodium and nadroparin calcium, on vasoconstriction in the human internal thoracic artery (ITA) in vitro. METHODS: Samples of redundant ITA segments obtained from 36 patients who underwent coronary artery bypass surgery were cut into 3mm wide rings and suspended in 20 ml organ bath. Activity of ITA rings precontracted with 80 mM KCl, 0.1 microM endothelin-1 (ET-1) and 1 microM norepinephrine (NE) after administration of enoxaparin and nadroparin in accumulative concentration ranging from 0.1 to 13.2 UI AXa/ml were recorded under isometric conditions by means of force transducers with digital output. The contraction after 80 mmol KCl, 0.1 microM ET-1 and 1 microM NE administration was treated as a control. RESULTS: Both studied LMWHs in concentration ranging from 0.12 to 13.2 UI AXa/ml did not change basal tonus and KCl precontracted ITA rings. When used in concentrations higher than 13.2 UI AXa/ml nadroparin but not enoxaparin significantly increased the tension in KCl precontracted arterial rings. In NE and ET-1 precontracted rings enoxaparin and nadroparin caused dose dependent relaxation without significant differences between both preparations. Incubation with nitric oxide blocker-Nomega-NITRO-L-ARGININE (L-NNA) in concentration 0.2 mM caused a significant attenuation of relaxant responses to both studied LMWHs in NE and ET-1 precontracted rings. CONCLUSION: LMWHs can have vasorelaxant effects on the receptor-mediated ITA vasoconstriction. The results suggest that LMWHs-induced relaxation in the human ITA is at least partially caused by nitric oxide release. Although the vasoactive effects are not the primary advantage of these drugs used as antithrombotics, such effects might have some clinical importance in the treatment and prophylaxis of graft spasm.