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Malignant melanoma (MM) is a cancerous transformation of melanocytes. It is a disease with the worst response to therapy and, compared to other malignancies, presents much earlier with metastases. MM still belongs to relatively late-detected malignant diseases. Even so, the MM mortality rate is up to 96% for a relatively small incidence (5%). The gold standard for MM diagnosis is a histopathological examination that requires invasive surgery. An invasive sampling method of a biological material can be a stressful factor for the patient, which is often the reason why patients do not seek medical assistance as soon as possible. Our goal was to find a link between metabolites in urine and the stage of MM. Two excitation peaks at 360–370 nm and 450 nm were characterised in spectra of urine samples. The emission spectra have shown one significant peak at 410–460 nm. After addition of glutathione reductase to the samples, fluorescence dropped down only in patient samples and hidden fluorophores appeared. Malignant diseases are associated with the presence of specific metabolites that can be detected fluorescently in biological material such as urine, which can be a suitable alternative for an early detection of cancer or for tracking changes during and after treatment.

Ischemic-reperfusion injury of the small intestine is an acute clinical condition with high mortality rate. This study describes the changes in levels of phenylalanine and tryptophan metabolites in intestinal homogenates and urine samples of Wistar male rats after 60 minutes of mesenteric ischemia and different reperfusion periods (1, 24, 30 hours) in comparison with a control group without the ischemia. The ischemic-reperfusion injury was quantified by the histopathological injury index. The levels of serotonin, epinephrine, and norepinephrine were determined in the intestinal homogenate and epinephrine, vanillylmandelic acid, and the 5-hydroxyindoleacetic acid was analyzed in urine using the HPLC method. The statistically significant increased level of serotonin, epinephrine and norepinephrine were detected in the intestinal samples after 24 hours of reperfusion (p

Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson's disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research., Competing Interests: Confiict of Interest The authors declare no confiicts of interest.

Background: Pancreatic carcinoma is one of the most severe oncological diseases of the gastrointestinal tract. At the time of diagnosis, up to 28% of patients have metastatic liver damage, and only 5% of patients survive five years. Scientific research focuses on non-invasive markers that could help screen for the disease and identify patients more quickly. Potential biomarkers also include matrix metalloproteinases, which play a role in oncogenesis., Material and Methods: We prospectively followed 46 patients with pancreatic cancer and benign pancreatic diseases from September 2022 to March 2023. We determined the level of MMP9 in serum and tissue biopsied during surgeries., Result: As a result, MMP9 levels were elevated from the T2 stage. The correlation between disease stage and MMP9 level was not confirmed in lower stages, possibly due to the small group of patients., Conclusion: MMP9 seems suitable for detecting late stages of pancreatic cancer, possibly for secondary prevention. We could not confirm a correlation between MMP9 levels and the initial stages of the disease (Tab. 1, Fig. 3, Ref. 21). Text in PDF www.elis.sk Keywords: pancreatic cancer, MMP9, marker, non-invasive, screening.

Cardiovascular comorbidities are independent risk factors for mortality in dialysis patients. MicroRNA signaling has an important role in vascular aging and cardiac health, while physical activity is a primary nonpharmacologic treatment for cardiovascular comorbidities in dialysis patients. To identify the relationships between muscle function, miRNA signaling pathways, the presence of vascular calcifications and the severity of cardiovascular comorbidities, we initially enrolled 90 subjects on hemodialysis therapy and collected complete data from 46 subjects. A group of 26 subjects inactiv group (INC) was monitored during 12 weeks of physical inactivity and another group of 20 patients exercise group (EXC) was followed during 12 weeks of intradialytic, moderate intensity, resistance training intervention applied three times per week. In both groups, we assessed the expression levels of myo-miRNAs, proteins, and muscle function (MF) before and after the 12-week period. Data on the presence of vascular calcifications and the severity of cardiac comorbidities were collected from the patients' EuCliD ® records. Using a full structural equitation modelling of the total study sample, we found that the higher the increase in MF was observed in patients, the higher the probability of a decrease in the expression of miR-206 and TRIM63 and the lower severity of cardiac comorbidities. A reduced structural model in INC patients showed that the higher the decrease in MF, the higher the probability of the presence of calcifications and the higher severity of cardiac comorbidities. In EXC patients, we found that the higher the increase in MF, the lower the probability of higher severity of cardiovascular comorbidities., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

AIM of the study was to compare serum levels of IGF-1, IGF-2 and insulin‑like growth factor‑binding protein 3 (IGFBP-3) among non‑obese and obese PCOS women, and to assess their relationship to metabolic and hormonal parameters.    METHODS: The study included 64 women diagnosed with PCOS (age 28.9 ± 5 years); 30 of them with BMI > 27 and 34 with BMI lower than 27. All subjects were examined for parameters of glucose and lipid metabolism, steroid hormones and serum IGF-1, IGF-2 and IGFBP-3 levels., Results: No significant differences in serum IGFBP-3 (p=0.534), IGF-1 (p=0.29) and IGF-2 (p=0.56) between two groups have been detected. IGFBP-3 was in positive correlation with total cholesterol (p=0.026), LDL cholesterol (p=0.03) and triacylglycerols (p=0.022). IGF-1 were negatively correlated with insulin (p=0.022), HOMA IR (p=0.033), triacylglycerols (p=0.0196) and waist circumference (p=0.049). A positive correlation was detected between IGF-1 and HDL cholesterol (p=0.025). No significant relationship was observed between IGF-1 and steroid hormones., Conclusion: Serum levels of IGF-1, IGF-2 and IGFBP-3 in obese PCOS women do not differ from those detected in non‑obese PCOS women. IGF-1 negatively correlated with metabolic parameters, indicating that lower IGF-1 may represent an important predictor of metabolic syndrome (MS) in PCOS women. All peptides seem to have little effect on ovarian steroidogenesis in PCOS (Tab. 1, Fig. 1, Ref. 30).

Background: Health characteristics associated with uric acid (UA) in the Roma minority remain less well known. The study sought to determine the ethnicity- and sex-specific associations of serum UA with health factors in Eastern Slovakian Roma and non-Roma populations. Methods: Data from the comparative cross-sectional HepaMeta study conducted in Slovakia in 2011 were used. The study enrolled 452 Roma subjects (35.2% men) and 403 non-Roma individuals (45.9% men) aged 18-55 years. Results: All study parameters differed between the sexes in both the Roma and non-Roma participants ( p < 0.05). UA was related to sex with odds ratio for female sex 0.873, 95% CI 0.853-0.893 ( p < 0.0001) per 10-unit increase of UA. Average level of UA ± standard deviation was lower in Roma than in non-Roma (226.54 ± 79.8 vs. 259.11 ± 84.53 umol/L; p < 0.0001). The Roma population presented with greater levels of high-sensitivity C-reactive protein (hsCRP) (3.07 ± 4 mg/L vs. 1.98 ± 2.83 mg/L; p < 0.0001) and ferritin in Roma males (403.78 ± 391.84 vs. 302.67 ± 236.26 mg/L; p < 0.0001). Conclusions: Serum UA is sex- and ethnicity specific. Elevated levels of hsCRP and ferritin particularly in Roma males can reflect low-grade systemic inflammation and thus serve as a marker of an increased cardiovascular risk., Competing Interests: The authors declare no conflict of interest.

The miRNA-206 and miRNA-23a play an important role in muscle tissue hypertrophy, regeneration and atrophy. Both of these miRNAs have been highlighted as promising adaptation predictors; however, the available evidence on associations is inconclusive. Therefore, our aim was to assess the expression levels of these two miRNAs as predictors of change in muscle function during strength training and physical inactivity among dialysed patients. For this purpose, 46 haemodialysis patients were monitored for 12-weeks of either intradialytic strength training (EXG, n = 20) or physical inactivity during dialysis (CON, n = 26). In both groups of patients, we assessed the baseline expression levels of miRNA-23a and miRNA-206 and the isometric force generated during hip flexion (HF) contraction before and after the 12-week period. Among the EXG group, the expression of miRNA-206 predicted the change in HF (R 2  = 0.63, p = 0.0005) much more strongly than the expression of miRNA-23a (R 2  = 0.21, p = 0.027). Interestingly, baseline miRNA-23a (R 2  = 0.30, p = 0.006) predicted the change in HF much more than miRNA-206 (p = ns) among the CON group. Our study indicates that the baseline expression of miRNA-206 could predict the response to strength training, while miRNA-23a could serve as a potential predictive marker of functional changes during physical inactivity in dialysis patients.

Introduction: Currently, just a few major parameters are used for cardiovascular (CV) risk quantification to identify many of the high-risk subjects; however, they leave a lot of them with an underestimated level of CV risk which does not reflect the reality., Material and Methods: The submitted study design of the Kosice Selective Coronarography Multiple Risk (KSC MR) Study will use computer analysis of coronary angiography results of admitted patients along with broad patients' characteristics based on questionnaires, physical findings, laboratory and many other examinations., Results: Obtained data will undergo machine learning protocols with the aim of developing algorithms which will include all available parameters and accurately calculate the probability of coronary artery disease., Conclusions: The KSC MR study results, if positive, could establisha base for development of proper software for revealing high-risk patients, as well as patients with suggested positive coronary angiography findings, based on the principles of personalised medicine., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Background : The aim of our work is to objectify the manner of transmission of HBV infection in young adult and middle-aged Roma people who live in the settlements. Methods : We used data from the cross-sectional study HepaMeta. We analyzed Roma people living in the settlements in East Slovakia, who have had HBsAg and anti HBc IgG antibodies examined. Results : We analyzed a cohort of 452 Roma participants with a mean of age 34.67 ± 9.14 years-159 (35.2%) were males. HBsAg positivity was diagnosed in 12.4% and the presence of anti HBc IgG antibodies was confirmed in 52% of participants. Prevalence of HBsAg positivity increases significantly with higher age, ( p = 0.026), as well as the presence of anti HBc IgG antibodies ( p < 0.0001). The prevalence of HBsAg positivity has doubled and anti HBc IgG positivity has tripled within two decades (<25 years vs. 35-45 years) in Roma settlements in East Slovakia. Conclusions : These findings allow us to express an opinion that horizontal transmission in adulthood may play an important role in the spreading of HBV infection.

Background : The Roma population is one of the largest marginalized population groups in Europe. The aim of our work was to summarize the morbidity of lifestyle-related diseases and infectious diseases in the Roma population living in segregated settlements. Methods : We used data from the cross-sectional study HepaMeta, in which we examined 452 Roma subjects with an average age of 34.7 ± 9.1 years, 35.2% of which were men, and 403 non-Roma subjects with an average age of 33.5 ± 7.4 years, 45.9% of which were men. We collected data by means of a questionnaire, anthropometric measures, and we analyzed blood and urine samples. Results : Roma subjects had a higher incidence of metabolic syndrome (RR: 1.478 (1.159-1.885), p < 0.0001), obesity or waist circumference >94 cm in men/80 cm in women (RR: 1.287 (1.127-1.470), p < 0.0001), and HDL-C < 1.03 mmol/L in men or <1.29 in women (RR: 2.004 (1.730-2.321), p < 0.0001) than their non-Roma counterparts. Subjects of the Roma population were more frequently diagnosed with kidney disease (RR: 1.216 (1.096-1.349), p < 0.0001), HBsAg positivity (RR: 4.468 (2.373-8.415), p < 0.0001), anti HBc IgG positivity (RR: 3.13 (2.598-4.224), p < 0.0001), and anti HEV positivity (RR: 2.972 (1.226-7.287), p < 0.0001). Serological markers of Toxoplasma gondii infection and Toxocara spp. were observed much more frequently among Roma than non-Roma subjects (RR: 1.868 (1.520-2.296), p < 0.0001, for Toxoplasma gondii ; and RR: 21.812 (8.097-58.761), p < 0.0001, for Toxocara spp.). Conclusions : Poor socio-economic conditions, an unhealthy lifestyle, and barriers precluding access to healthcare are factors that affect the Roma population in settlements and lead to an increased prevalence of metabolic syndrome and its components, kidney disease, viral hepatitis B and E, and some parasitic diseases.

Background: Intradialytic resistance training (IRT) protects patients' muscle mass and functions against protein-energy wasting, malnutrition and cachexia. However, the evidence of the effects of such an intervention in haemodialysis patients is limited and not conclusive. To improve the applicability of such interventions, we need a better understanding of molecular, functional and psycho-social adaptation in dialysed patients following a physical training. Therefore, the aim of this study is to investigate the effects of IRT on lower extremity muscle functions, quality of life, and anxiety and depression, clinical outcomes and circulatory micro-ribonucleic acid (miRNA) profiles in patients on chronic haemodialysis therapy., Methods: We will perform a quasi-experimental study in 3 dialysis centres. Patients will be recruited via their nephrologists and will be allocated to an experimental and a control group based on the location of the patients' dialysis centre. Patients allocated to the experimental group will undergo a 12-week IRT, while the control group will remain physically inactive during dialysis. The primary outcome is the change in the maximal force produced during an isometric contraction of lower extremity muscles. Secondary outcomes regard quality of life, anxiety and depression, clinical outcomes and circulatory miRNA profiles. Patients' level of health literacy defined as the ability to get and understand health information will be also measured in the study as a potential modifier of effects., Discussion: This quasi-experimental study can add in an important way to our understanding of the effects of resistance training on dialysis patients' muscle strength, quality of life and disease-specific outcomes.

Background : The Roma population is one of the major marginalized groups in Europe, having higher incidence of all spectrums of disease and a shorter life expectancy. Yet, the reasons for higher morbidity and its exact prevalence were not properly studied. Objectives : The objective of our study was to compare the frequency of metabolic syndrome (MetS) in Roma people to the non-Roma population in Slovakia, and to compare levels of uric acid and its correlation with components of metabolic syndrome. Methods : A group of 452 Roma people aged 18⁻55 years, was compared to a control group of 403 non-Roma people. The data were obtained by questionnaire, anthropometric measures, and analyzed blood and urine samples Results : The prevalence of MetS was significantly higher among Roma participants (131; 29.6%) compared with non-Roma participants (80; 20.1%), p = 0.001. Roma people significantly more often fulfilled obesity and low high-density lipoprotein (HDL) criteria of MetS (257, 58.9% vs. 180, 45.8%, p < 0.0001, and 312, 70.0% vs. 140, 34.9%, p < 0.0001). There was no difference in the triacylglycerols (TG), glycemia or blood pressure (BP) criteria of MetS. The Roma also presented with greater levels of high sensitivity C-reactive protein (hs-CRP). Baseline levels of uric acid (UA) among the Roma population were significantly lower compared with the majority population (226.54 ± 79.8 vs. 259.11 ± 84.53) ( p < 0.001). The levels of UA significantly correlated with fulfilled criteria of MetS. Univariate regression showed that UA is a significant predictor of MetS in the whole cohort (unadjusted odds ratio (OR) 1.005; 95% CI 1.004⁻1.007; p < 0.0001) also after the adjustment for age, sex, and ethnicity (adjusted OR 1.008; 95% CI 1.005⁻1.010; p < 0.0001). Conclusions : We were able to show that prevalence of MetS among the Roma is higher than in the majority population. Moreover, the uric acid levels are significantly lower in the Roma group as well as when it comes to a cohort with MetS. Levels of UA, besides others, depend on ethnicity, age, and sex.

Prevalence of Hepatitis B is relatively low in developed European countries. However specific subpopulations may exist within each country with markedly different Hepatitis B burden. Roma minority is very numerous in Slovakia and their lifestyle is completely different to non-Roma population. The aim of this study is to map Hepatitis B prevalence in Roma and compare it to non-Roma population and to explore potential socio-economic and health related risk factors. Cross-sectional epidemiology study was performed in Slovakia that included randomly sampled Roma population and geographically corresponding random sampled non-Roma population. Comprehensive questionnaire about risk factors was administered and blood samples were drawn for Hepatitis B serology and virology tests. Altogether 855 participants were included. Global Hepatitis B surface Antigen (HBsAg) positivity rate was 7.7% (i.e., active Hepatitis B) and anti Hepatitis B core IgG antibody (antiHBcIgG) positivity rate was 34.6%. Roma population had significantly higher prevalence of Hepatitis B, both active chronic infection (12.4%; 95% Confidence Interval (CI) 9.58%⁻15.97% versus 2.8%; 95% CI 1.56%⁻4.91%; p < 0.0001) and antiHBcIgG positivity (52.8%; 95% CI 48.17%⁻57.44% versus 25.9%; 95% CI 12.56%⁻20.02%; p < 0.0001) Main risk factors for HBsAg positivity were Roma ethnicity, male sex and tattoo., Conclusion: There is a very high prevalence of Hepatitis B in Roma communities in Slovakia, with potential for grave medical consequences.

Background: A hundred years ago, scientists believed that amniotic fluid is a yellowish hypotonic mixture of foetal urine and maternal transudate with peculiar odour. Current knowledge shows that it represents a dynamic, complex mixture of inorganic and organic compounds., Objectives: Despite modern technological procedures, information is still lacking about the composition and properties of amniotic fluid. We focused on dynamics of selected physical and chemical properties of the amniotic fluid with the increasing gestational week., Methods: The physicochemical characteristics of 89 amniotic fluid samples were determined according to the week of pregnancy. The determination of pH, specific gravity, glucose and nitrites was performed immediately, at room temperature., Results: Our results show a significant negative correlation between week of pregnancy and semi-quantitative determined parameters of specific gravity (p < 0.001), pH (p < 0.01) and glucose (p < 0.001) values. Within the whole group of samples (n = 89), 29 % (n = 26) were nitrites positive (N+) and 71 % (n = 63) nitrites negative (N-)., Conclusion: In this study were determined basic parameters of amniotic fluid, which could be related to a wide range of pathological states (Tab. 2, Fig. 1, Ref. 27).

Background: This study describes the effect of rapid tumor growth of patients suffering from various grades of malignant ductal breast carcinoma associated with the gene expression of ECM protein emilin 1, in correlation with the number of gene copies of emilin 1 and degradation of tumor tissue proteins., Methods: A total of 40 examined patients participated in the experiment (controls, n = 10, grades GI-GIII, each n = 10). After isolation of total mRNA, transcription of mRNA into the cDNA was performed. Quantification of gene expression changes was detected by the real-time PCR method. Analysis at the protein level was performed via Western blot method., Results: During the detection of changes at the mRNA level, a significantly decreased level of emilin 1 in tumor tissues with grade II (about 54 ± 8 % lower than control) was identified. Protein-level analysis indicated an increased level of emilin 1 in tumors with grade I in comparison with control samples (about 10 ± 3 %)., Conclusion: Obtained results demonstrated that the suppressive role of emilin 1 is related to the grade of growing breast tumors, and associated with increased hypoxia in the tumor microenvironment followed by elevated unfolding and degradation of tissue proteins.

Clinical diagnosis of gynaecological malignancies is usually successful in the advanced stages of the tumour, and this has a major impact on the success of therapy. Therefore, in the last few years, cancer research has tried to identify and characterise new biochemical and molecular markers needed as predictive indicators for the diagnosis of cancer. Our aim has been to search the molecular changes in gene expression of death receptor 6, glycoprotein M6B (Gpm6B) and genes associated with tumours of the female genital system. After isolation of messenger RNA (mRNA), transcription of mRNA into the cDNA was performed. The quantification of gene expression changes was detected using the reverse transcription polymerase chain reaction (RT-PCR) method. Analysis at the protein level was performed using the Western blot method. In both methods, we used actin as a housekeeping gene for normalisation. Numerical quantification of changes in expression and in the level of the specific proteins was evaluated using the Data Syngene program. Significant changes in the levels of protein and mRNA expression were detected, mainly in the death receptor 6 (Dr6) gene of patients suffering from cancer of the corpus and cervix uteri and ovarian cancer, which also corresponded with the level of protein Dr6. At the level of transcription, a significant increase in the expression levels of mRNA for the Gpm6B gene was detected, which led to an increase in corresponding protein in the peripheral blood of patients with gynaecological tumours against the healthy control group. This article could help to find an adequate marker for clinical application that will enable more sensitive detection of the early stages of gynaecological malignancies from the peripheral blood of patients.

Background: In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma., Materials and Methods: We compared expression of genes related to apoptosis (DR6 and Gpm6B) in the blood of patients suffering from stage I of breast cancer in different grades (I-IV), with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot., Results: In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1) and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower., Conclusion: This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

Objective: We have evaluated the impact of chronic administration of clorgyline, a potent monoamine oxidase A inhibitor and a former antidepressant, on the preimplantation embryo development in Wistar rats., Material and Methods: Females were injected intraperitoneally daily for 30 days with saline (control animals, C), or with a low dose of clorgyline (0.1 mg/kg/day, LDC) or with a high dose of clorgyline (1 mg/kg/day, HDC). Embryos were isolated on day 5 of pregnancy and their urine was collected., Results: The number of embryos per female did not differ between experimental groups and control, but we have recorded a decreased number of embryos in HDC group compared to LDC (p < 0.05). We have found that LDC significantly reduced the presence of healthy embryos and increased the presence of the degenerated embryos (p < 0.001). The administration of the LDC resulted in the lowest cell number in blastocysts (p < 0.01). Concerning monoamines in urine, we have observed significantly increased serotonin levels in HDC group compared to control (p < 0.05) and LDC animals (p < 0.01). Norepinephrine levels in both experimental groups were significantly elevated compared to controls, too (p < 0.001 LDC vs C; p < 0.01 HDC vs C)., Conclusions: We assume that the impaired embryo development recorded in the LDC group after clorgyline administration was a consequence of the higher levels of the norepinephrine. We speculate that lesser negative effect of HDC compared to LDC on the preimplantation embryo development could be the consequence of the lesser norepinephrine levels and/or elevated serotonin levels (Tab. 2, Fig. 2, Ref. 37). Full Text in free PDF www.bmj.sk.

The aim of the study was to investigate the mechanism of action of somatostatin analogues (SSA), ionizing radiation, and their combination on pituitary adenoma cells with special emphasis on proliferative and apoptotic activity. In the 14 GH-secreting adenomas pretreated with SSA before surgery, more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis than in the reference group of 17 unpretreated adenomas. The proliferative Ki-67 labeling index was significantly lower in the treated group (median 1.6 per 1000) than in the untreated patients (median 5.0 per 1000). Apoptosis was detected in only 2 of the 14 pretreated adenomas, and it was more frequent (9/17) and more prominent in the untreated group. In cell lines, the SSA had minimal antiproliferative effect, and they were unable to induce apoptosis. Ionizing radiation at doses of 5-20 Gy induced apoptosis in the corticotroph cell line AtT20 with no cell-cycle block. In the somatotroph GH3 cell line, the early (premitotic) apoptosis was detectable using only a high dose of 200 Gy; after irradiation with doses of 20-50 Gy, apoptosis appeared with the latency of 48-72 hours, and was preceded by cell-cycle arrest in the G(2)/M phase. The treatment with somatostatin-14 during irradiation increased the percentage of apoptotic cells in culture 10 days after irradiation (11% versus 3% using 20 Gy).

With the aim to investigate histopathological changes and proliferative and apoptotic activity in GH-secreting adenomas we compared 14 cases pre-treated with somatostatin analogues before surgery with a reference group of 17 un-pretreated ones. Besides routine histology, immunocytochemical detection of all pituitary hormones, caspase-3, cytokeratin-18, and "M30 antigen", its apoptosis-specific fragment was performed. Proliferation activity of the tumour was determined by the Ki-67 antigen expression. In treated adenomas more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis. The Ki-67 labelling index was lower in treated group (mean 2.5, median 1.6 per mille) than in untreated patients (mean 9.4, median 5.0 per mille). The difference was statistically significant (p=0.049 using Mann-Whitney Rank Sum Test). Apoptosis was detected in only 2 of the 14 pre-treated adenomas, and it was more frequent (9/17) and more prominent in the untreated group.

The aim of the study was to determine the inhibitory effects of somatostatin analogues with relative specificity to somatostatin receptor subtype 2 (SSTR2) (BIM-23197), subtype 5 (SSTR5) (BIM-23268), and their combination on GH and PRL secretion in acromegalic adenomas in vitro. Three types of answer were observed: 1. In one resistant adenoma no inhibition was achieved. 2. The GH secretion in six adenomas was suppressed significantly more (p < 0.01 or p < 0.001 using Mann-Whitney U-test in concentration range of 10(-12) to 10(-8) mol/l) with SSTR2 specific analogue BIM-23197 with no additive effect of compounds combination. 3. In three adenomas the potency of BIM-23197 and BIM-23268 was almost equal and the combination of these SSTR2 and SSTR5 specific compounds had statistically significant additive effect (p < 0.05 or p < 0.01 in concentration range of 10(-12) to 10(-8) mol/l). PRL secretion of five adenomas was more suppressed with SSTR5 specific BIM-23268 (statistically significant in concentrations 10(-10) to 10(-8) mol/l). In conclusion the somatostatin analogue BIM-23268 had an additive effect on suppression of GH secretion in a subset of adenomas, where both SSTR2 and SSTR5 were involved. This effect was not observed in the majority of tumours, where the inhibitory effect seems to be mediated via SSTR2 only.

The authors have studied the susceptibility of two key protective enzymes, glutathione peroxidase (GPX) and glutathione reductase (GR) to the reactive oxygen species (ROS) known to induce oxidative damage in vitro system containing Fe2+/EDTA. The ability of ROS scavanger stobadine to prevent oxidative damage was also studied. Incubation of GPX with Fe2+/EDTA resulted in the significant decrease in its enzyme activity while under the same condition the activity of GR was not changed. The presence of stobadine was effective in protecting GPX from the loss of its activity by in vitro oxidizing agents. The monitoring of the mitochondrial outer membrane dynamics by the method of synchronous fluorescence fingerprint showed that the membrane is involved in these processes. (Fig. 3, Ref. 35.)

The study investigated the prooxidative in vitro effect of various Fe(2+)-EDTA concentrations on biochemical parameters of the energetic metabolism of rat liver mitochondria. Fe(2+)-EDTA was added in concentrations 150, 300 and 400 mmol/mg of mitochondrial protein. The study included the investigation of consumption of oxygen in state 4 (without ADP addition) and in state 3 (with ADP addition), and the activities of ATP-ase, superoxide dismutase (SOD) and glutathione reductase. The mitochondrial outer membrane dynamics were simultaneously monitored by the method of synchronous fluorescence fingerprint. When compared with the control group, the results imply that in state 4, the addition of 150 mmol of Fe2+/mg of mitochondrial protein caused an insignificant increase in respiration to 104%, whereas in state 3, the oxygen consumption was insignificantly inhibited to 82%. The activity of ATPase was insignificantly raised to 105%, whereas the superoxide dismutase activity has decreased significantly to 77%. The activity of glutathione reductase increased significantly to 124%. The addition of 300 mmol of Fe2+/mg of mitochondrial protein has caused a significant inhibition of oxygen consumption to 67% in state 4 and to 31% in state 3. The activity of ATPase showed an insignificant elevation to 104%. The activity of superoxide dismutase was significantly reduced to 52% and that of glutathione reductase dropped to 72%. The addition of 400 Fe2+/mg of mitochondrial protein strongly diminished the oxygen consumption to 36% in state 4, and similarly to 37% in state 3. The activity of ATP-ase was significantly decreased to 39%, the superoxide dismutase activity diminished to 17% and glutathione reductase activity dropped to 37%. The monitoring of the mitochondrial outer membrane by the analysis of synchronous fluorescence fingerprint showed that the membrane is involved in these processes. (Fig. 5, Ref. 12.)