Novel strategies for treatment of pulmonary arterial hypertension.

Pulmonary hypertension (PH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. Special population include patents with pulmonary arterial hypertension (PAH). A greater understanding of the epidemiology, pathogenesis, and pathophysiology of PAH has led to significant advances over the past few years. Modern drug therapy provides a significant improvement in patient symptomatic status and a slower rate of clinical deterioration. Despite this, PAH remains a chronic disease without a cure. There is a need for the development of novel therapies and therapeutic strategies, as treatment options are neither universally available nor always effective, possibly due to the large number of mediator and signaling pathways with downstream effectors which are implicated in the pathobiology of PH, and which are not fully reversed during PAH therapy. In the following pages, we review novel strategies for treatment of PAH. For this purpose we summarized the role of specific drug therapies that involve: endothelin receptor antagonists (ERA), phosphodiesterase type 5 inhibitors (PDE-5i) and prostacyclin and prostanoids (PGI2). We focused on novel molecular mechanisms in PAH of recently approved: Guanylate cyclase stimulator and non-prostanoid IP receptor agonist. We discussed novel approach to combined therapy, as well as a new generation of investigational drugs and promising PAH-associated signaling pathways, such as, PDGF, RhoA/ROCK RAAS, HT-5 and others.

Errors in reporting on dissolution research: methodological and statistical implications.

OBJECTIVE: In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. METHODS: The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. RESULTS: Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. DISCUSSION AND CONCLUSION: A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

WHAT MOTIVATES POLISH COMMUNITY PHARMACISTS TO PURSUIT OF POSTGRADUATE EDUCATION?.

Due to increasing importance of the advisory role for physicians and patients played by the pharmacist over the last decade, it seems appropriate to evaluate if and why pharmacists are interested in postgraduate medical education. The purpose of the study was to develop and validate an instrument to assess such motives, with special interest to Polish community pharmacists. A self-administered questionnaire was completed by a sample of participants of community pharmacist specialization programs and it was analyzed in relation to participants of other postgraduate courses. They were asked to rank their motives on a Likert-like scale and the underlying dimensions for study motives were identified using exploratory and confirmatory techniques. The reasons for taking specialization for community pharmacists were similar as compared to participants of other postgraduate studies. However, the autotelic factor was not so strong and the crucial reason was that such postgraduate training was required to be promoted in work. Basing on Polish results, we propose the division of motives into three groups - autotelic, instrumental and coincidental. The validated self-administered questionnaire based on this division displayed acceptable construct validity and internal consistency, and therefore can be proposed as an example tool to assess the particular motives and expectations of potential postgraduate students and employees in the pharmaceutical job market. The promotion of postgraduate education among pharmacists can improve the quality of pharmaceutical service.

MOTIVATIONS SURROUNDING THE PURSUIT OF A PHARMACY CAREER - THE CASE OF POLISH STUDENTS.

The objective was to examine the motivation for studying pharmacy. A self-administered questionnaire, developed and validated by the authors, was completed by a sample of 414 Polish pharmaceutical students (Year I - Year 5). The students ranked their motives on a Likert-like scale and their underlying dimensions were identified using exploratory and confirmatory techniques. Several socio-demographic variables and future pharmaceutical career plans were-also identified. The reliability and validity of the proposed questionnaire were confinued. Factor analysis revealed three factors determining the choices of the respondents: coincidental, instrumental and autotelic. Two of the top three reasons for studying pharmacy were autotelic. A relatively small percentage of respondents chose a pharmaceutical education due to coincidence. The motivation for choosing a pharmaceutical career remained relatively stable among students of all the study years. The practice point of our survey can be that, basing on Polish case, we,propose the validated self-administered questionnaire that displays acceptable construct validity and internal consistency, and can serve as an example tool to assess the particular motives and expectations of potential students and employees in the pharmaceutical area.

[Current issues in etiology, diagnostics and management in pulmonary hypertension].

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions characterizing with by an abnormal increase in mean pulmonary arterial pressure. It is a rare, debilitating disease with a poor prognosis. Despite significant progress in diagnosis and management, including disease-targeted therapies as well as development of specialized centres, PH remains a chronic disease without a cure. If untreated, it leads to right heart failure and premature death, and a multifactorial pathomechanism impacts negatively on further prognosis. Insufficient social awareness or non-specific initial symptoms accompany to delayed diagnosis and specialist treatment. In the following pages, we will review the currently classification, etiology as well as and diagnostic algorithms in PH. We discuss approved treatments, especially specific dug therapy for pulmonary arterial hypertension, and recently approved strategies for its refund. We also summarize the general measures for patients and their caregivers, as well as the role of support groups, and specialized centers in Poland.

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro.

BACKGROUND: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). MATERIALS AND METHODS: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. RESULTS: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. CONCLUSIONS: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis.

The use of biodegradable polymers in design of cellular scaffolds.

The objective of this work was to demonstrate the usage of biodegradable polymers, made of calcium alginate and dibutyrylchitin, in the design of cellular scaffolds having broad application in reconstructive therapy (dentistry, orthopedics). To visualize cells seeded on calcium alginate and dibutyrylchitin polymers DAPI staining of fibroblasts nuclei was used. The cytotoxicity of the materials and microscopic evaluation of the viability of seeded cells was tested with a PKH 67 fluorescent dye. To assess the cellular toxicity the proliferation of fibroblasts adjacent to the tested polymers was examined. The vitability of cells seeded on polymers was also evaluated by measuring the fluorescence intensity of calcein which binds only to live cells. The conducted experiments (DAPI and PKH 67 staining) show that the tested materials have a positive influence on cell adhesion crucial for wound healing - fibroblasts. The self-made dibutyrylchitin dressing do not cause the reduction of viability of cells seeded on them. The in vitro study illustrated the interactions between the tested materials, constructed of calcium alginate or dibutyrylchitin and mouse fibroblasts and proved their usefulness in the design of cellular scaffolds. Examined polymers turned out to be of great interest and promise for cellular scaffolds design.

The placental transfer of erythromycin in human pregnancies with group B streptococcal infection.

OBJECTIVES: The aim of this study was to investigate the effectiveness of erythromycin in preventing fetal and intrauterine group B streptococcal (GBS) infections. The study evaluated the penetration of erythromycin through the placenta, by comparing umbilical vein and maternal serum erythromycin concentrations. MATERIAL AND METHODS: The study subjects were 42 pregnant women, with GBS-positive screening or whose laboratory screening was not available, who delivered between 17th April 2013 and 22nd July 2013. The women were given 600 mg of erythromycin intravenously. After delivery blood was drawn from the mother's antecubital vein and umbilical cord vein. Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. The percentage and correlation between umbilical vein and maternal serum erythromycin concentration were calculated. Based on regression function parameters selected factors: maternal age, maternal body weight, gestational age at delivery related to the umbilical vein serum erythromycin concentration, were investigated. Results: A total of 42 umbilical vein-maternal serum pairs were included in the analysis. The mean umbilical vein-maternal serum erythromycin concentration percentage was 2.64 ± 1.55%. There was a moderate correlation between umbilical vein serum and maternal serum erythromycin concentration. Pregnancy complications and selected variables of mothers in control group had no effect on the serum erythromycin concentration in the umbilical vein. CONCLUSIONS: Intravenous application of erythromycin at a dose of 600 mg, allowed to achieve therapeutic concentration in maternal serum. However, when it comes to placental transfer of erythromycin, the lack of therapeutic concentration in umbilical vein serum was observed. The limited transplacental transfer of erythromycin, which was approximately 2.6%, suggests compromised efficacy in the treatment of intrauterine fetal infections. On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when erythromycin is used exclusively to treat maternal infections.

[Evaluation of erythromycin concentration in the umbilical artery serum]. / Ocena stezenia erytromycyny w surowicy krwi z tetnicy pepowinowej.

OBJECTIVES: The aim of the study was to investigate the effectiveness of erythromycin in preventing intrauterine infection caused by group B streptococcus (GBS). MATERIAL AND METHODS: The study included 20 pregnant women with GBS-positive screening or whose laboratory screening was not available, who delivered between April 17, 2013 and July 22, 2013. The women were given 600 mg of erythromycin intravenously After delivery blood was drawn in parallel from maternal antecubital vein and umbilical cord artery Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. Statistical analysis for measurable and non-measurable characteristics were performed, correlation coefficients for each pair of variables were calculated in order to investigate the sought dependence. RESULTS: Mean placental transfer of erythromycin was 2.04%. There was a high correlation between umbilical artery serum and maternal serum erythromycin concentration. Selected variables of mothers in the control group had no effect on serum erythromycin concentration in the umbilical artery CONCLUSIONS: Transplacental transfer of erythromycin is limited (2.04%). Intravenous application of erythromycin at a dose of 600 mg does not allow to achieve the value of MIC50 and MIC90 for erythromycin against strains S. agalactiae in umbilical artery serum, what suggests a compromised efficacy in the treatment of intrauterine fetal infections. At the same time, the placenta seems to be an effective barrier reducing fetal exposure when this macrolide is used to treat maternal infections.

Concurrent rho-kinase and tyrosine kinase platelet-derived growth factor inhibition in experimental pulmonary hypertension.

BACKGROUND: We hypothesized that inhibition of Rho-kinase by fasudil, together with tyrosine kinase platelet-derived growth factor (PDGF) receptor inhibition by imatinib, results in greater pulmonary arterial hypertension (PAH) improvement. METHODS: The effects of such regimens were investigated on hemodynamics, right ventricle hypertrophy, PDGF and ROCK in experimental monocrotaline (MCT)-induced pulmonary hypertension. Fourteen days after MCT injection, male rats were treated orally for another 14 days with imatinib, fasudil or their combination. RESULTS: Concurrent imatinib and fasudil administration reversed an MCT-induced increase in right ventricular pressure more than either drug alone and decreased right ventricle hypertrophy (right ventricle weight to left ventricle plus septum weight ratio) significantly. The simultaneous administration of fasudil and imatinib caused a further decrease in plasma PDGF-BB levels compared to either drug alone. CONCLUSIONS: Inhibition of Rho-kinase by fasudil in addition to tyrosine kinase PDGF inhibition by imatinib can result in further PAH improvement. Such outcome may result from additional impact of the Rho-kinase inhibitor on the decrease in PDGF-induced effects.

Comparative tolerability of targeted therapies in pulmonary hypertension.

Introduction: The objective of this study was to estimate the safety profile of pulmonary hypertension-specific therapies using placebo-controlled and active comparator trials. Material and methods: The search corpus comprised Medline, Scopus, Embase and Clinical Trials databases. A systematic review and meta-analysis was performed to assess the relative risk of severe events and discontinuations as well as of adverse drug reactions (ADRs) classified into 26 categories and 21 subcategories defined by the Medical Dictionary for Regulatory Activities (MedRA). Results: Pulmonary hypertension-specific therapies had the greatest effect on such events as flushing and headache as well as jaw pain, limb pain and myalgia or gastrointestinal disorders. The relative risk for ADRs in patients receiving monotherapy (vs. placebo/supportive therapies) and combined regimens (vs. monotherapy) was significantly increased. The risk of cessation for the combined regimen was slightly higher (Qinter-group, p = 0.0778). Such ADRs as blood and lymphatic system disorders with the anemia subgroup, gastrointestinal disorders with diarrhea and nausea subgroups, respiratory and thoracic diseases or nervous system disorders with headache tended to occur more often in combination regimens as compared to monotherapy. Conclusions: About half of the main categories and subcategories of adverse reactions according to MedRA were associated with a relatively high frequency and hazard ratio. Their risk can be increased when combination regimens are used, especially.

The beneficial impact of fasudil and sildenafil on monocrotaline-induced pulmonary hypertension in rats: a hemodynamic and biochemical study.

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Serum adiponectin, resistin, leptin concentration and central adiposity parameters in Barrett's esophagus patients with and without intestinal metaplasia in comparison to healthy controls and patients with GERD.

BACKGROUND/AIMS: Central obesity is a risk factor for GERD, Barrett's esophagus and esophageal adeno-carcinoma. Recent studies have suggested that adipocytokines are the possible link between adiposity and Barrett's carcinogenesis. To determine the adiponectin, resistin and leptin concentration as well as the central adiposity parameters in BE patients with and without intestinal metaplasia (IM) in comparison to GERD and healthy controls. METHODOLOGY: Total of 77 patients (30 patients with GERD, 26 BE with IM and 21 BE without IM) and 30 healthy controls were investigated for the central obesity parameters. Serum levels of adipocytokines were measured with ELISA. RESULTS: The serum concentration of adiponectin was significantly lower in BE compared to those in GERD and to controls (p<0.001). Levels of leptin was slightly higher in BE than in GERD and controls (NS). Level of resistin was significantly higher in GERD compared to both control and BE patients (p<0.001). Waist circumference, WHR and WTR were significantly higher in BE patients compared to GERD (p<0.001) and to control group (p<0.001). CONCLUSIONS: Features of central obesity rather than BMI are associated with BE development. Adipokines may be important at the early step of BE development, before the IM occurrence.

Concomitant administration of different doses of simvastatin with ivabradine influence on PAI-1 and heart rate in normo- and hypercholesterolaemic rats.

Ivabradine is a novel heart rate lowering agent that inhibits I(f) ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg × kg(-1) bw) with ivabradine (10 mg × kg(-1) bw) during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving 20 mg × kg(-1) bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of 20 mg × kg(-1) bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone. Conclusion. The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders.

Effects of Implementing Personalized Health Education in Ambulatory Care on Cardiovascular Risk Factors, Compliance and Satisfaction with Treatment.

Aim and Methods: Data from the CARDIOPLUS study (a prospective, multicenter, non-interventional study, which was conducted among patients and physicians from ambulatory patient care in Poland) were used to assess whether primary care behavioral counseling interventions to improve diet, increase physical activity, stop smoking and reduce alcohol consumption improve outcomes associated with cardiovascular (CVD) risk factors, metabolic parameters, compliance and satisfaction with treatment in adults. The study was carried out throughout Poland in the period from July to December 2019. Results: The study included 8667 patients­49% women and 51% men aged (63 ± 11 years)­and 862 physician-researchers. At the 3-month follow-up, there was a significant reduction in body weight (p = 0.008); reduction of peripheral arterial pressure, both systolic (p < 0.001) and diastolic (p < 0.001); reduction in total cholesterol levels (p < 0.001), triglycerides (p < 0.001), and LDL cholesterol (p < 0.001). The percentage of respondents who fully complied with the doctor's recommendations increased significantly. The respondents assessed their own satisfaction with the implemented treatment as higher (by about 20%). Conclusions: As a result of pro-health education in the field of lifestyle modifications, a significant reduction of risk factors for cardiovascular diseases, as well as improved compliance and satisfaction with pharmacological treatment, was observed. Thus, appropriate personalized advice on lifestyle habits should be given to each examinee in a positive, systematic way following the periodic health check-ups in order to reduce the person's risk and improve the effectiveness of the treatment.

Elevated resistin opposed to adiponectin or angiogenin plasma levels as a strong, independent predictive factor for the occurrence of major adverse cardiac and cerebrovascular events in patients with stable multivessel coronary artery disease over 1-year follow-up.

BACKGROUND: Adipokines such as adiponectin and resistin, as well as angiogenin, may be associated with inflammation and atherosclerosis. The relationship between their levels and prognosis in high risk patients is, however, still unclear. The aim of this study was to evaluate the prognostic value of these adipokines in patients with stable multivessel coronary artery disease (MCAD). MATERIAL/METHODS: The study group comprised 107 MCAD patients (74% males, mean age 63 ± 8 years). Adiponectin, resistin and angiogenin plasma levels were measured at admission and after 1-year follow-up. Primary end point (major adverse cardiac and cerebrovascular events--MACCE) was defined as cardiac death, nonfatal myocardial infarction, stroke, and hospitalization for angina or heart failure over a 1-year period. RESULTS: After 1-year follow-up, 9 (8%) patients died, all from cardiovascular causes. Primary end point was experienced by 32% of patients. Surgical treatment (CABG) was received by 51% of patients, while 49% were treated medically alone. Total cholesterol concentration levels ≥ 173 mg/dl were associated with a 7-fold increase (OR 7.3; 95% CI, 1.6-33.0); LDL ≥ 93.5 mg/dl with a 16-fold increase (OR 16.3; 95% CI, 2.8-93.8), and resistin ≥ 17.265 ng/ml with a 13-fold increase in MACCE risk (OR 13.5; 95% CI, 2.3-80.3). In multivariate analysis, a medical treatment strategy (p = 0.001), a higher CCS class (p = 0.004), resistin levels (p = 0.003) and a higher Gensini score (p = 0.03) were independent predictors of MACCE. CONCLUSIONS: In stable patients with MCAD, elevated plasma resistin (as opposed to adiponectin or angiogenin) is a strong, independent predictive factor for the occurrence of MACCE over 1-year follow-up.

Reporting experimental studies on animals - The problems with translating of outcomes to clinical benefits. Methodological and statistical considerations: The example of pulmonary hypertension.

The variability inherent in animal models and the methods used to define drug response can lead to highly divergent results when evaluating new drug candidates. Several guidelines exist for high-quality and comprehensive reporting of experiments with animals. The present survey makes a quantitative demonstration of whether compliance with good preclinical practice guidelines can affect the results and reduce risk of over- or underestimation of treatment benefit. This meta-analysis was performed on more than 400 animal studies concerning pulmonary hypertension, where a wide range of potential therapeutic agents have been recently positively assessed in preclinical experiments. The experiments were reviewed according to the selected methodological and statistical items being recommended to report in papers. A quantitative evaluation was performed of their impact on effect size, which defined the efficacy of particular drug candidates. In addition, the paper also examines whether the quality score calculated for the papers included in the analysis changed over the previous 25 years. In conclusion, some information in experimental studies is often missed or incomplete, which complicates the correct evaluation and comprehension of obtained results. This in turn could subsequently increase the potential hazards involved in translating positive experimental outcomes to possible clinical benefits in patients.

Different modes of delivery and hormonal stress response.

OBJECTIVES: The aim of the study was to determine how the type of delivery affects the stress response cycle and the level of cortisol, progesterone and corticoliberin. MATERIAL AND METHODS: The study was conducted among 26 pregnant women admitted to the Gynecology and Obstetrics Ward due to an approaching delivery date or the onset of labor. The participants were aged between 20 and 41 years, with a mean age of approximately 30 years. After delivery, blood was drawn in parallel from the maternal antecubital vein, the umbilical cord vein and the umbilical cord artery. The levels of stress hormones were assessed by ELISA. The results were subjected to statistical analyses, and correlation coefficients were calculated for individual variable pairs. The analysis also examined the participation of pregnant woman in antenatal education. RESULTS: A high correlation was observed between cortisol and progesterone levels in venous and arterial cord blood and physiological delivery. The mean cortisol level was 247.37 ng/mL in venous cord blood and 233.59 ng/mL in arterial blood and the respective mean progesterone levels were 331.81 ng/mL and 342.36 ng/mL. The highest cortisol concentration was determined in the primiparas umbilical cord blood (236.182 ng/mL in the vein, 230.541 ng/mL in the artery). Correlation between cortisol level in venous and arterial cord blood and prenatal education was also noted (venous cord blood: r = -0.5477; F = 10.2833; p = 0.0038; cord arterial blood: r = -0, 4436; F = 5.8789; p = 0.0232). CONCLUSIONS: The results obtained emphasize the importance of the hypothalamic-pituitary-adrenal (HPA) axis as one of the potential mechanisms actively involved in childbirth. The determined levels of cortisol and progesterone in the maternal and umbilical cord blood varied significantly depending on the type of delivery, with higher concentrations being observed in the case of natural delivery. In addition, the highest levels of cortisol were determined in primiparas; however, lowered umbilical cord blood cortisol levels were observed in pregnant women who had participated in antenatal education, regardless of the number of deliveries.

Quality of life in high-risk patients with stable multivessel coronary artery disease treated either medically or with coronary artery bypass graft surgery - 12-month follow-up.

BACKGROUND: Treatment of chronic diseases, such as atherosclerosis, usually leads to significant short-term improvement. Mid- and long-term results are not always as satisfactory. That is why improvement of quality of life should be the leading qualification criterion for invasive procedures, which sometimes carry a risk of complications. AIM: To determine the quality of life in patients with stable, multivessel coronary artery disease (MCAD), treated surgically or medically. METHODS: The study group comprised 107 patients (pts; 80 males) suffering from MCAD, assigned to coronary artery bypass grafting (CABG) (55 pts) or to medical treatment alone (52 pts). The mean Gensini score in the whole group was 90 (66-132). To evaluate quality of life we used a Short Form-36 (SF-36) health status survey by the International Quality of Life Assessment Project. RESULTS: During a 12-month follow-up 9 pts died (6 pts in the medically treated group and 3 in the CABG group), all for cardiovascular reasons. Patients treated conservatively were more often hospitalised due to angina symptoms (20 vs. 5, p = 0.003). Analysis of SF-36 showed that pts treated surgically had better improvement of quality of life in comparison with medically treated patients. Significant differences were found for physical functioning, bodily pain, vitality, mental health and mental component summary. CONCLUSIONS: This study has shown that there is a significant difference in health-related quality of life 12 months after CABG surgery and medical treatment alone in high-risk patients with MCAD. Surgical treatment decreases the number of adverse events, better attenuates of anginal and heart failure symptoms, and improves the quality of life, especially the mental component. Our results should encouraged selecting patients with advanced atherosclerosis for revascularisation procedures, even if there is a very high peri-procedural risk.

Stability studies of expired tablets of metoprolol tartrate and propranolol hydrochloride. Part 1. Content determination.

In recent years the growing interest in drug stability problem has been observed. The stability of pharmaceutical products seems to play an important role from the economical point of view. However, there are not many studies that reported about the stability of drugs past their expiration dates. The objective of the current study was to determine tablet content of expired tablets and tablets with expiry date has not been exceeded. The analyzed tablets contained metoprolol tartrate (50 mg) and propranolol hydrochloride (10 mg), respectively. Content determination was performed using HPLC method with UV detection. The proposed method was validated with regard to linearity, sensitivity, intermediate accuracy and precision. No discrepancies between the results of determination and the declared values range for all the analyzed tablets were observed. The results of performed study might suggest that storage of analyzed batches of tablets over time period exceeding the expiry date given by the manufacturer did not influence their contents.