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Fermented rapeseed meal has the potential to partial replace soybean meal in feed mixtures for poultry without a negative impact on the health condition and performance of birds. This is due to the fact that the fermentation process can reduce the amount of antinutritional factors, improve the use of nutrients and impart probiotic properties to rapeseed meal. Therefore, this study was undertaken to investigate the effect of fermented rapeseed meal on the performance, egg quality, intestinal morphometry, the viscosity of intestinal content and total phosphorus availability. A total of 108 Lohmann Brown laying hens at 26 wk of age were used in the 90-day study. All hens were randomly divided into 3 treatment groups, with 12 replicates (cages) each, as follows: control group received no rapeseed meal, the URSM group received 3% unfermented rapeseed meal and the FRSM group received 3% fermented rapeseed meal. In the case of performance, egg traits, sensory evaluation of eggs, the viscosity of intestinal content and the availability of total phosphorus, if the distribution was normal, a 1-way analysis of variance was performed. If the distribution was not normal, the Kruskal-Wallis test was performed. In the case of histomorphometric evaluation of the intestine, if the distribution was normal, the Student t test for independent samples was performed. If not, a Mann-Whitney U test was performed. The performed analyses showed that the supplementation of fermented rapeseed meal had no negative effect on the performance of birds and the quality of eggs. Fermented rapeseed meal was also associated with improved histomorphometric parameters of the small intestine compared to the group receiving unfermented rapeseed meal in the feed. Laying hens from FRSM group were characterized by significantly lower viscosity of intestinal content (P < 0.05) compared to URSM group. Phosphorus in FRSM group was significantly more available to the birds (P < 0.05) compared to URSM group. These results suggest that supplementation with fermented rapeseed meal may be beneficial, especially in times of unstable prices of soybean meal and problems with its availability., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The naiads, large freshwater mussels (Unionida), have very long life spans, are large-bodied, and produce thousands to millions of larvae (glochidia) which typically must attach to host fish tissues to metamorphose into a juvenile mussel. Glochidia develop within a female's marsupial gill demibranch, thus their number is restricted by female size. However, larger mussels acquire more energy, which could be invested in either larger-sized glochidia, in a more glochidia, or a combination of both. The high level of host specialization seen in many naiads may constrain glochidial size and shape around a narrow optimum, while naiads that use a wide range of host fishes may be predicted to possess greater plasticity in glochidial morphology. In this paper, we investigated the relationship between maternal body size and progeny body size and shape, aided by modern digital microscopy. We analyzed the between- and within- species variation of glochidia size and shape relative to female size in four widespread species of European naiads: Anodonta anatina, Anodonta cygnea, Unio crassus and Unio tumidus. Whereas the total reproductive output is collinear with female body size, substantial differences between species in glochidia size were found within genus Anodonta, but not genus Unio where glochidial size is remarkably consistent. The glochidial shape, however, differed within both Unio and Anodonta. We interpret this constant within-species glochidial size in Unio as reflecting a constraint imposed by the likelihood of successful transmission onto and off from a narrow range of hosts, whereas their shape seems to be less constrained. The Anodonta species, inhabiting a wide spectrum of habitats and using more than twice the number of fish hosts than Unio spp., have larger glochidia with greater variation in size and shape. Our results suggest that measures of glochidial variability may also serve as an indicator of host specificity in other naiads., (© 2021. The Author(s).)

The lungs are a common site of metastases from malignant tumors. Their removal with a minimal but safe tissue margin is essential for the long-term survival of patients. The aim of this study was to evaluate the usefulness of a 1940 nm thulium-doped fiber laser (TDFL) and a 1470 nm diode laser (DL) in a pig model of lung surgery that involved the incision and excision of lung tissue. Histopathological analysis was performed on days 0 and 7 after surgery. Neither TDFL nor DL caused significant perioperative or postoperative bleeding. Histological analysis revealed the presence of carbonized necrotic tissue, mixed fibrin-cellular exudate in the superficial zone of thermal damage and bands of deeper thermal changes. The mean total width of thermal damage on day 0 was 499.46 ± 61.44 and 937.39 ± 109.65 µm for TDFL and DL, respectively. On day 7, cell activation and repair processes were visible. The total width of thermal damage was 2615.74 ± 487.17 µm for TDFL vs. 6500.34 ±1118.02 µm for DL. The superficial zone of thermal damage was narrower for TDFL on both days 0 and 7. The results confirm the effectiveness of both types of laser in cutting and providing hemostasis in the lungs. TDFL caused less thermal damage to the lung parenchyma than DL.

Purpose: Healing of osteoporotic defects is challenging and requires innovative approaches to elicit molecular mechanisms promoting osteoblasts-osteoclasts coupling and bone homeostasis., Methods: Cytocompatibility and biocompatibility of previously characterised nanocomposites, i.e Ca 5 (PO 4 ) 3 OH/Fe 3 O 4 (later called nHAp/IO) functionalised with microRNAs (nHAp/IO@miR-21/124) was tested. In vitro studies were performed using a direct co-culture system of MC3T3-E1 pre-osteoblast and 4B12 pre-osteoclasts. The analysis included determination of nanocomposite influence on cultures morphology (confocal imaging), viability and metabolic activity (Alamar Blue assay). Pro-osteogenic signals were identified at mRNA, miRNA and protein level with RT-qPCR, Western blotting and immunocytochemistry. Biocompatibility of biomaterials was tested using bilateral cranial defect performed on a senescence-accelerated mouse model, ie SAM/P6 and Balb/c. The effect of biomaterial on the process of bone healing was monitored using microcomputed tomography., Results: The nanocomposites promoted survival and metabolism of bone cells, as well as enhanced functional differentiation of pre-osteoblasts MC3T3-E1 in co-cultures with pre-osteoclasts. Differentiation of MC3T3-E1 driven by nHAp/IO@miR-21/124 nanocomposite was manifested by improved extracellular matrix differentiation and up-regulation of pro-osteogenic transcripts, ie late osteogenesis markers. The nanocomposite triggered bone healing in a cranial defect model in SAM/P6 mice and was replaced by functional bone in Balb/c mice., Conclusion: This study demonstrates that the novel nanocomposite nHAp/IO can serve as a platform for therapeutic miRNA delivery. Obtained nanocomposite elicit pro-osteogenic signals, decreasing osteoclasts differentiation, simultaneously improving osteoblasts metabolism and their transition toward pre-osteocytes and bone mineralisation. The proposed scaffold can be an effective interface for in situ regeneration of osteoporotic bone, especially in elderly patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Marycz et al.)

The main aim of the study was to assess the risk of falls, and physical fitness in the group of women aged 60 to 65 years of age suffering from an identified osteoporosis in comparison to a similar group of healthy women. The main question was: What is the level of physical fitness and risk of fall among women with osteoporosis compared to healthy women? The research included 262 women aged 60 to 65 of age: 135 with osteoporosis and 127 healthy ones, living in the Małopolskie and the Świętokrzyskie Provinces of Poland. To assess the level of physical fitness, the Senior Fitness Test (SFT) was used, while the Tinetti POMA (Performance Oriented Mobility Assessment) and Timed Up&Go test (TUG) were used to asses the risk of fall. Significant statistical differences in average results of physical fitness assessment were noticed as regards the following aspects: flexibility of the lower body part p < 0.001; flexibility of the upper body part p < 0.001. Essential differences were demonstrated in assessing the risk of falling with p < 0.01. Women with osteoporosis are marked by a lower physical fitness than healthy women. A higher percentage of great and serious risk of fall was demonstrated among women with osteoporosis., (© 2021. The Author(s).)

The aim of this study was to develop and assess a polyvinyl alcohol-cellulose derivatives-based film with incorporated povidone-iodine (PVP-I) predicted for applications in the treatment of periodontitis. Films were fabricated by solvent-casting, and their physical characteristics, such as their surface and structure morphology, mechanical properties, and disintegrating time, were evaluated. For in vitro iodine release studies and evaluation, the antimicrobial activity was tested using a modified disc diffusion method against five microbial strains. For further use, we selected the film with polyvinyl alcohol-hydroxypropyl methylcellulose (PVA/HPMC&#95;B) based on acceptable physicochemical properties. To assess the subacute toxicity of the film composition, the tissue regeneration process was tested in rats and compared to a conventional dressing commonly used in wound healing (Spongostan). Seven days after implantation, dorsal skin sections and blood samples (n = 10, in total n = 30) were examined. The wound area, epithelium, and dermis were evaluated microscopically, while the blood collected from the rats underwent biochemical analysis. The blood biochemistry results were comparable in all three groups. No significant histological differences between the Spongostan and the placebo film developed after subcutaneous implantation were observed. In contrast, the inflammation stage was reduced and the "scar" in the dermis was smaller when PVP-I and PVA/HPMC&#95;B films were used. A smaller local inflammatory response inflicted less tissue damage, leading to the activation of subsequent regeneration phases and restoration of the area to its original state. The results obtained confirmed that PVP-I incorporated into PVA-hydroxypropyl methylcellulose film is a promising drug carrier, working faster and more effectively than the other two dressing materials evaluated. These developments provide a promising alternative in tissue regeneration and the wound healing process.

Although eutrophication of freshwaters is a natural process, the human impact often leads to inland waters becoming overloaded with nutrients, impoverishing many valuable and vanishing habitats, such as floodplain lakes. These changes need to be reversed if the occurrence of endangered aquatic species is to be restored. In this paper we analyse the impact of a change in the water regime of a naturally eutrophic floodplain lake, which harbours a large diversity of Unionidae (large freshwater mussels), a globally threatened taxonomic group that provides important ecosystem functions and services. We found that a slight increase in the discharge from this waterbody, following the construction of an additional outflow pipe, positively influenced recruitment in three of the five mussel species inhabiting the lake. We also found that, after the construction of this additional outflow, the niches of juveniles of Anodonta cygnea and Unio spp. changed, revealing differences in their hydrological requirements. Our results suggest that, as in lotic habitats, complex hydraulic parameters are highly significant to unionid mussels in lentic conditions., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Bleeding is a major complication of anticoagulation in acute pulmonary embolism (APE) while estimating individual bleeding risk remains challenging. Elevated D-dimer levels (DD) have been shown to predict bleeding events., Objectives: (1) direct comparison of the capacity of bleeding risk prediction scores (VTE-BLEED, RIETE, HAS-BLED, HEMORR 2 HAGES) to prognosticate in-hospital bleeding events in the acute phase of APE in a real-life population of APE patients;(2) augmentation of the discriminative capacity of fore mentioned scores with DD., Materials: Post-hoc analysis of a prospective observational study. DD levels were measured using the VIDAS D-dimer Exclusion test. Receiver operating characteristic curves, areas under the curve (AUC) for bleeding prediction were calculated for scores and DD. Bleeding scores+DD were compared using an established index quantifying the reclassification of patients (net reclassification index, NRI)., Results: 310 APE patients were included. 35(11.3%) bleeding events occurred (hematomas, GI, urinary tract, retroperitoneal, uterine, CNS, respiratory tract): 17 major (MB) and 18 clinically-relevant non-major bleedings (CRNMB), none were fatal. All scores had satisfactory AUCs (0.754-0.767), except HAS-BLED (AUC = 0.512; 0.455-0.569). DD were higher in patients with bleeding events (29,911 ng/ml vs. 4805 ng/ml, p = .031), AUC 0.621(0.520-0.721), p = .02. DD = 5750 ng/ml was characterized by OR = 2.3(95%CI 1.05-5.0) for all bleeding events. Adding DD improved the discriminatory capacity of tested scores in the non-high risk of bleeding category, NRI 0.07-03., Conclusions: Of the tested scores RIETE, HEMORR 2 HAGES, VTE-BLEED performed best at identifying APE patients at risk of in-hospital bleeding complications. DD levels may predict in-hospital bleeding events and may improve identifying patients classified as non-high risk who experience bleeding complications., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This article discusses the influence of phenology-related intraseasonal asynchrony on metapopulation dynamics and stability. As the part played by intraseasonal asynchrony is as yet unclear and poorly described, greater account of it should be taken in both metapopulation research and conservation practice. The subpopulations of the Parnassius mnemosyne metapopulation studied here are strongly isolated because of the phenological shift between them, despite the relatively small physical distances between them. This isolation is the result of a significant temporal shift in the species' flight periods in the main metapopulation centers: in some seasons its flight times in the different subpopulations did not overlap at all. The predicted results of such strong intraseasonal asynchrony are not altogether clear. On the one hand, they reduce the vulnerability of the entire metapopulation to the effects of short-term random disasters. On the other, the ever-greater isolation of subpopulations may cause the metapopulation to become a nonequilibrium one, which will have a serious impact on its long-term survival., (© 2018 Institute of Zoology, Chinese Academy of Sciences.)

Introduction: Increased values of emerging fat indices are correlated with increased cardiovascular risk., Aim: To examine the novel non-invasive predictors of coronary disease, namely the carotid extra-media thickness (EMT), PATIMA, and epicardial adipose tissue (EAT), in a group of patients with morbid obesity., Material and Methods: We examined a group of 40 morbidly obese (OB) patients and a control group (CG). All patients were subjected to anthropometric measurements, as well as laboratory and ultrasound examinations., Results: EATmean and EMTmean differed significantly between groups (OB vs. CG): 5.09 vs. 3.50 and 808.50 vs. 737.00, p < 0.0001, respectively., Conclusions: Strong correlations were found between novel non-invasive predictors of coronary disease, namely the carotid extra-media thickness, PATIMA, and epicardial adipose tissue. The above-mentioned fat indices were not found to correlate significantly with BMI or other body weight-related parameters used to assess the adipose tissue content. Further studies are required., Competing Interests: The authors declare no conflict of interest.

Background: Conflicts occur in intensive care units (ICUs), and an international multicentre study conducted in 2008, including 323 ICUs from 24 European countries, confirmed the occurrence of this phenomenon. There are no data in Poland. The aim of the study was to analyse the frequency of the occurrence of conflicts in ICUs in Polish hospitals, and their most frequent sources., Methods: The study was based on an original questionnaire performed in 12 ICUs in the Pomeranian Voivodship. The respondents were asked questions regarding the frequency, type, and lines of conflicts between employees, as well as potential causes of conflicts., Results: Completed surveys were received from 232 employees, including 79 doctors and 153 nurses. The phenomenon of occurrence of conflicts was confirmed by about 30% of the staff, providing answer that conflicts occur "often". About 43% of staff estimated that conflicts "sometimes" occur and 25% chose the answer "rarely". Analysis of the answers made it possible to identify the most common potential causes of conflict., Conclusions: The main sources of conflicts in ICUs appear to be external factors such a financial issues and physical overload. The hospital policy and the health policy of the state are also important. The perceived conflicts require careful and constant monitoring. The frequency of hidden conflicts requires thorough assessment of their impact on the quality of work.

Bioethics was created in the 70s of the last century. From this period come works written by Van Resselaer Potter and André Hellegers, in which the authors raised the issue of the need to discuss the progress and to define a new reflection, they used for the first time in the scientific literature the term bioethics. In the United States of America, as well as in European countries, institutions began to emerge in which scientific bioethical reflection was realized. In Poland in the 1970s, the socio-political situation was not conducive to the integration of scientific circles or the freedom of exchange of views. Significant progress in the field of medicine, emerging new treatment options, posed questions that had to be answered. The questions were formulated in different environments, including by doctors who themselves participated in the progress of medical sciences, introducing, for example, new increasingly aggressive treatments, or saw new challenges emerging in the medical profession, which were not regulated by the hitherto applied principles of classical medical ethics. The article describes the achievements of prof. Jan Nielubowicz, prof. Józef Bogusz and prof. Tadeusz Kielanowski in the creation of Polish bioethical regulations in the field of experimental research in humans, the activity of prof. Kornel Gibińki in the formation of Bioethics Commisions, contribution of prof. Stefan Raszeja and prof. Marek Sych in bioethical education of the society and the role of prof. Krzysztof Szczygieł in the creation of the first Polish scientific bioethical unit., (© 2018 MEDPRESS.)

Freshwater mussels of the order Unionida provide important ecosystem functions and services. Unfortunately, some previously widespread species are now seriously endangered. To restore the historical range of the population of Unio crassus in the Biała River, southern Poland, the species was reintroduced into a series of 'stepping stones' joining two remnant populations. During the first phase of the study, the relationships between the abundance of U. crassus, physical habitat, and water quality were studied to assess reintroduction potential. In general, chemical water quality improved upstream from the existing population, favouring the decision for reintroduction, whereas morphological variables worsened. Mussel abundance was correlated negatively with the elevation and slope of channel, organic matter contents, and pH (exceeding 8.0), but positively with silt presence, water conductivity, and concentrations of HCO 3 - , Ca 2+ , and NO 3 - . During the second phase, adult individuals were introduced into one type of functional habitat-marginal channel sectors with still water and fine sediment. Despite the initial very high rate of reproduction in some parts of the upper reach of the river, the juveniles were ultimately recruited only in the lower part of the restored range, resulting in a very rapid change in recruitment at a channel slope of 1.8‰. Recruitment was positively related to silt content, conductivity, and Ca 2+ and HCO 3 - ions, negatively to channel elevation and slope, and water pH. The host fish species showed no correlation with abiotic habitat features within the studied reach. These results imply that most of the habitat traits related to U. crassus occurrence depended on the river's longitudinal profile, not on the chemical water quality, and that final success of introduction should be evaluated after several years., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aim: Patients with acute pulmonary embolism (APE) associated with hemodynamic instability, i.e. high-risk APE (HR-APE), are at risk for early mortality and require urgent reperfusion therapy with thrombolysis or embolectomy. However, a considerable proportion of HR-APE subjects is not reperfused but only anticoagulated due to high bleeding risk. The aim of the present study was to assess the management of HR-APE in a single large-volume referral center., Methods: A single-center retrospective study of 32 HR-APE subjects identified among 823 consecutive patients hospitalized for symptomatic APE., Results: Out of 32 subjects with HR-APE (19 women, age 69 ± 19 years), 20 patients were unstable at admission and 12 subsequently deteriorated despite on-going anticoagulation. Thrombolysis was applied in 20 (62.5%) of HR-APE subjects, limited mainly by classical contraindications in the remainder. Percutaneous pulmonary embolectomy was performed in 4 patients. In-hospital PE-related mortality tended to be higher, albeit insignificantly, in the patients who developed hemodynamic collapse during the hospital course compared to those unstable at admission (67% vs. 40%, p = 0.14). Also, survival was slightly better in 22 patients treated with thrombolysis or percutaneous embolectomy in comparison to 10 subjects who received only anticoagulation (54% vs. 40%, p = 0.2). Major non-fatal bleedings occurred in 7 of 20 patients receiving thrombolysis (35%) and in 2 (17%) of the remaining non-thrombolysed 12 HR-APE subjects., Conclusions: Hemodynamically instability, corresponding to the definition of HR-APE, affects about 4% of patients with APE, developing during the hospital course in approximately one-third of HR-APE subjects. As almost 40% of patients with HR-APE do not receive thrombolytic therapy for fear of bleeding, urgent percutaneous catheter-assisted embolectomy may increase the percentage of patients with HR-APE undergoing reperfusion therapy. Further studies are warranted for a proper identification of initially stable intermediate-risk APE subjects at risk of hemodynamic collapse despite appropriate anticoagulation.

Background: Cells adapt to hypoxia by transcriptional induction of genes that participate in regulation of angiogenesis, glucose metabolism and cell proliferation. The primary factors mediating cell response to low oxygen tension are hypoxia inducible factors (HIFs), oxygen-dependent transcription activators. The stability and activity of the α subunits of HIFs are controlled by hydroxylation reactions that require ascorbate as a cofactor. Therefore, deficiency of intracellular vitamin C could contribute to HIFs overactivation. In this study, we investigated whether vitamin C content of human thyroid lesions is associated with HIF-1α and HIF-2α protein levels., Methods: Expression of HIF-1α and HIF-2α as well as vitamin C content was analyzed in thyroid lesions and cultured thyroid carcinoma cell lines (FTC-133 and 8305c) treated with hypoxia-mimetic agent (cobalt chloride) and ascorbic acid. The expression of HIFs and hypoxia-induced glucose transporters were determined by Western blots while quantitative real-time PCR (qRT-PCR) was performed to detect HIFs mRNA levels. Ascorbate and dehydroascorbate levels were measured by HPLC method., Results: We found an inverse correlation between vitamin C level and HIF-1α but not HIF-2α expression in thyroid lesions. These results agree with our in vitro study showing that vitamin C induced a dose - dependent decrease of HIF-1α but not HIF-2α protein level in thyroid cancer cells FTC-133 and 8305C. The decreased HIF-1α expression was correlated with reduced expression of hypoxia-related glucose transporter 1 (GLUT1) in thyroid cancer cells., Conclusion: The results demonstrate that HIF-1α activation is associated with vitamin C content in thyroid lesions. Our study suggests that high tumor tissue ascorbate level could limit the expression of HIF-1α and its targets in thyroid lesions.

Significant recovery of discussion about the need for the formulation of criteria of death was provoked due to the progress of medicine. Development of anaesthesiology and intensive therapy, introduction of new resuscitation techniques and devices, which are increasingly better able to maintain and sometimes even replace functions of the respiratory or cardiovascular system, which are essential for the survival meant that existing for centuries, socially accepted classical criteria of death, based on cessation of breath and circulation, are no longer sufficient. The criteria of brain death developed by the Ad Hoc Committee - 12-experts commission at Harvard University, published in Journal of American Medical Association in August 1968 and were the breaking point. The concept has been adopted and accepted by society in many countries soon, while in Poland the process of formulating and introduction of criteria for brain death took much more time. Based on the available literature and preserved archival materials, this article describing the process of development of new death criteria, acceptance by the National Team of Specialists and publication in 1984 the announcement by the Minister of Health and Social Welfare about the criteria of brain death.

The first open-heart surgery in Gdansk took place in 1975. It was possible thanks to the gift of a Pemco extracorporeal circulation machine from the Netherlands to the Surgery Institute of the Medical Academy of Gdansk. The article presents additional, unpublished informations which enable a new interpretation of the previously known facts.

Cancer cells exhibit an altered metabolism characterized by enhanced glycolysis and glucose consumption. In glucose‑addicted cancer cells upregulation of glucose transport across the plasma membrane is mediated by a family of facilitated glucose transporter proteins, particularly glucose transporter 1 (GLUT1). The aim of the present study was to investigate the impact of GLUT1 expression on glucose uptake and viability of FTC-133 and 8305c thyroid cancer cells growing in hypoglycemic, normoglycemic and hyperglycemic conditions. The results showed that the total expression of GLUT1 was higher in the two cell types growing in low glucose compared to cells growing in normoglycemia or hyperglycemia and this was correlated with AKT Ser473 phosphorylation but not with the expression of hypoxia inducible factor α (HIF1α). However, the membrane expression of GLUT1 was correlated with HIF1α expression. HIF1α expression was positively correlated with the glucose concentration in FTC-133 cells, whereas this expression was inversely correlated in 8305c cells. Glucose uptake was dependent on the membrane level of GLUT1 but not total GLUT1 expression. Downregulation of GLUT1 expression by RNAi in FTC-133 cells caused a reduction in glucose uptake but did not significantly affect cell viability. In the case of 8305c cells showing low endogenous GLUT1 expression and lack of HIF1α expression in normoxic conditions GLUT1 RNAi impacted cell viability. These data suggested that GLUT1 may be part of an AKT1-dependent mechanism allowing cells to survive in low levels of glucose. Glucose concentration inversely affected HIF1α expression and the level of GLUT1 in membrane as well as glucose uptake in FTC-133 and 8305c cells. The extent of GLUT1 impact on cell viability was also cell-type-dependent.

Enhanced glucose requirement of cancer cells is associated with an increased glucose transport across plasma membrane that is mediated by a family of facilitated glucose transporter proteins, named GLUTs. GLUT1 is the main transporter in thyroid cancer cells. Glucose is the principal physiological substrate of GLUT1; however, it is also capable of transporting of oxidized form of vitamin C [i.e., dehydroascorbic acid (DHAA) which inside the cells is reduced to ascorbic acid (AA)]. The objective of this study was to determine the effect of normo-, hypo-, and hyperglycemia conditions on GLUT1-dependent intracellular ascorbate accumulation and viability of thyroid cancer cells. GLUT1 seems to be the main DHAA transporter in thyroid cancer cells because its knockdown by RNAi reduced DHAA accumulation by more than 80%. The results showed that in thyroid cancer cells high glucose inhibits both transport of AA and DHAA. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate.

Background: Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals., Methods: We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed., Results: Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p < 0.030), low-density lipoprotein cholesterol ( 3.28 mmol/L vs. 2.90 mmol/L, p < 0.032), and non-high-density lipoprotein cholesterol ( 3.74 mmol/L vs. 3.25 mmol/L, p < 0.016) levels, in addition to lower fasting glucose levels ( 4.51 mmol/L vs. 4.81 mmol/L, p < 0.042). A positive correlation between fasting glucose and insulin levels (r = 0.28; p < 0.015) was detected in the fhMetS participants. Higher mean daytime systolic blood pressure (121.5 mmHg vs. 113.3 mmHg, p < 0.035), mean daytime diastolic blood pressure ( 79.0 mmHg vs. 74.5 mmHg, p < 0.045), and mean nighttime diastolic blood pressure ( 64.0 mmHg vs. 59.5 mmHg, p < 0.019) were observed in the fhMetS group., Conclusions: More than 50% of the fhMetS participants had excess weight or a lipid disorder, which may indicate an increased risk of cardiovascular disease and the need for regular ambulatory assessment of serum lipid concentrations in young people with a family history of MetS.

First codes of medical ethics appeared between 18th and 19th century. Their formation was inspired by changes that happened in medicine, positive in general but with some negative setbacks. Those negative consequences revealed the need to codify all those ethical duties, which were formerly passed from generation to generation by the word of mouth and individual example by master physicians. 210 years has passed since the publication of "Medical Ethics" by Thomas Percival, yet essential ethical guidelines remain the same. Similarly, ethical codes published in Poland in 19 century can still be an inspiration to modem physicians.

The enhancement of glucose metabolism in neoplastic cells is mediated by the overexpression of key glycolytic enzymes and glucose transporters (GLUTs). In particular, an increased expression of hypoxia-related GLUT1 and GLUT3 has been found in a variety of malignancies. The aim of this study was to examine the expression levels of GLUT1 and GLUT3 in benign and malignant thyroid tumors, as well as in non-neoplastic lesions. Analysis of the mRNA expression levels of solute carrier family 2, member 1 (SLC2A1) and solute carrier family 2, member 3 (SLC2A3) (genes coding GLUT1 and GLUT3, respectively) was performed by the real-time PCR method with fluorescent probes. GLUT1 and GLUT3 protein expression levels were determined in thyroid specimens by immunodetection after separation of proteins on 10% polyacrylamide slab gels and electrotransfer onto Immobilon-P membranes. The majority of papillary carcinoma samples showed a higher expression of GLUT1 and GLUT3 in comparison with follicular carcinoma cases and non-neoplastic thyroid lesions. A tendency towards an increased expression of GLUT1 and GLUT3 was observed in papillary carcinoma cases with more advanced disease stages. Moreover, a significant correlation was noted between the hypoxia-related GLUT1 and GLUT3 expression determined by both methods. In conclusion, our findings suggest that GLUT1 and GLUT3 play an important role in the pathology of thyroid glands.

Malignant cells are known to enhance glucose metabolism, to increase glucose uptake and to inhibit the process of oxidative phosphorylation. Accelerated glycolysis is one of the biochemical characteristics of cancer cells that allow them to compensate the inefficient extraction of energy from glucose in order to continue their uncontrolled growth and proliferation. Upregulation of glucose transport across the plasma membrane is mediated by a family of facilitated glucose transporter proteins named GLUT. Overexpression of GLUTs, especially the hypoxia-responsive GLUT1, has been frequently observed in various human carcinomas. Many studies have reported a correlation between GLUT1 expression level and the grade of tumor aggressiveness, which suggests that GLUT1 expression may be of prognostic significance. Therefore, GLUT1 is a key rate-limiting factor in the transport and glucose metabolism in cancer cells. This paper presents the current state of knowledge on GLUT1 regulation as well as its utility in the diagnosis and therapy of cancers.

Insulin significantly influences Ca(2+) signals evoked by various stimulants. In type 1 recent onset diabetes mellitus the proliferative response of T cells is significantly decreased. The number of clinical trials exploring the role of anti-CD3 monoclonal antibodies (mAb) as a therapeutic agent in recent onset diabetes mellitus type 1 is increasing last years. Therefore, a better understanding of the interplay between T cell receptor (TCR) dependent Ca(2+) increase, and insulin is of vital clinical significance. The aim of the study was to assess the effect of insulin on TCR evoked Ca(2+) responses in T lymphocytes obtained from healthy volunteers and patients suffering from long lasting diabetes mellitus type 1. Analysis was performed with use of the flow cytometer. We demonstrated that T cells ability to mobilize Ca(2+) was significantly reduced in long lasting diabetes mellitus type 1. Ca(2+) decrease achieved by the long term incubation with anti-CD3 mAb in T cells from healthy volunteers was restored by insulin. Strong interrelationship between baseline Ca(2+) level and plateau phase response to TCR stimulation was observed in the cytoplasm of cells pre-incubated with insulin from both healthy subjects and diabetic patients (r = 0.95, p < 0.0001 and r = 0.94, p < 0.0001, respectively). We postulate the existence of the interplay between TCR mediated activation and insulin. The TCR-insulin interplay is blunted in long lasting diabetes mellitus type 1. These observations may have an important implication for future therapeutic options in diabetes.

The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show different distribution and have non-redundant functions. The aim of this study was to determine whether the expression, phosphorylation, and localization of Akt1 isoform in human thyroid malignant lesions are different from those in benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue samples and Western blot method was used to detect Akt1 presence in both cellular fractions. Akt1 expression was also assessed by ELISA method. To estimate Akt1 phosphorylation, kinase was immunoprecipitated from cell lysates and tested with anti-phospho-Akt antibodies. The Akt1 expression in majority of thyroid cancer samples was significantly higher than in benign lesions (p < 0.05). Akt1 both in differentiated cancers (follicular and papillary) and benign lesions was localized mainly in cytoplasmic fraction. In two of three anaplastic cancer samples Akt1 was predominantly localized in nucleus. The ratio of phosphorylated Akt1 to total Akt1 was lower in cancers than in non-neoplastic lesions and adenomas. Thus, although Akt1 seems to be overexpressed in thyroid neoplasms, its high phosphorylation is not characteristic for thyroid cancers.

O-GlcNAcylation is a common and dynamic modification of intracellular proteins in which β-N-acetyl-glucosamine moieties are attached to hydroxyl groups of serine or threonine residues (O-GlcNAc). Accumulating evidence suggests the critical role of protein O-GlcNAcylation in signal transduction, transcriptional control, cell cycle regulation and protein degradation. However, the exact role of O-GlcNAc modification in tumor pathogenesis or progression remains to be established. In the present study, we investigated the effect of increased O-GlcNAcylation of cellular proteins on IGF‑1 signaling in 8305C thyroid anaplastic cancer cells. The global O-GlcNAc level in the 8305C cells was increased by down-regulation of β-N-acetyl-D-glucosaminidase (O-GlcNAcase) activity, an enzyme which removes O-GlcNAc moieties. We demonstrated here that IGF‑1 stimulates Akt1 activity in 8305C cells, and down-regulation of O-GlcNAcase activity by the chemical inhibitor PUGNAc or RNA interference method enhances this effect. Increased Akt1 activation increased cell proliferation. In cells with down-regulation of O-GlcNAcase activity, kinase GSK3β phosphorylation and cyclin D1 levels were higher than those in control cells. Our findings suggest that increased proliferation of 8305C cells treated with PUGNAc or RNAi against O-GlcNAcase at least partially depends on the IGF‑1-Akt1-GSK3β-cyclin D1 pathway.

RNA interference is one of the most important discoveries in the field of molecular biology. To date, many studies have been reported which suggest that RNA interference takes part in various biological processes essential for the development of many diseases. On the other hand, owing to its high specificity and efficiency, RNA interference has become a powerful tool in gene therapy. However, introduction of small interfering RNAs (siRNAs) to a target tissue requires overcoming some critical biological barriers. This, in turn, contributes to searching for new effective vectors, which should selectively penetrate the tissue and be able to exclude the innate immune response. This study provides a brief overview of the application of RNA interference in the diagnosis and therapy of some human diseases.

Objectives: Noninvasive fetal RHD genotyping from maternal plasma of RhD(/-) pregnant women of Caucasian race may be used for predicting the risk of hemolytic disease because the RHD gene is usually absent in such populations. If detected in plasma of such women, the RHD gene originates from the RhD(+) fetus. The number of fetal copies of the gene in maternal plasma is extremely small. In the presented case of the RhD(/-) pregnant woman with anti-D it was impossible to give a fetal RHD result due to mother's RHD(+) genotype. The fetal RHD was determined from amniocytes., Aim: to present the difficulties related to the interpretation of results of invasive and noninvasive procedures., Material and Methods: whole blood, plasma and amniotic fluid of the RhD(-) woman with anti-D (14 week of pregnancy) as well as whole blood of the newborn. RHD and RHCE*c were genotyped by real-time PCR in DNA isolated from maternal plasma and amniocytes and the RHD and d-genotypes were tested by SSP methods in DNA isolated from whole blood and amniocytes., Results: RHD and RHCE*c were detected in DNA isolated from plasma. The high level of RHD suggested its origin from the mother's DNA therefore it was impossible to determine the fetal RHD. The d-little test identified a RHD(IVS3+ 1G>A) variant in the mother's genome. A weak signal of real-time PCR for the RHD was obtained in amniocytes but the RHD was not detected by SSP. The RHCE*c was detected by both methods. Results were inconclusive; the fetal RHD status remained unknown. The child was RhD(-) with RHD in its DNA undetected by either method., Conclusions: 1/The RHD(IVS3+ 1G>A) variant in the RhD(-) mother precluded formal noninvasive fetal RHD genotyping. 2/Real-time PCR is too sensitive for amniocyte testing and may lead to false results as it detects trace maternal DNA in amniotic fluid. 3/The frequency of RHD(IVS3+1G>A) occurrence in Poland requires further studies.

Hyperglycaemia increases inflammatory cytokine concentration in the blood. Elevated levels of interleukin-18 (IL-18), a cytokine belonging to the interleukin-1 (IL-1) family, were recently reported in patients with Type 2 diabetes mellitus (DM2) and nephropathy. The aim of the present work was an examination of IL-18 concentration in the sera of elderly DM2 patients with nonproliferative retinopathy and age-matched control people and an estimation whether this cytokine plays pro- or anti-angiogenic role in in vivo angiogenic activity of their sera in mice cutaneous angiogenesis test. Recombinant human IL-18 injected intradermally to murine skin induced significant neovascular reaction. DM2 patients sera contained higher concentration of IL-18 and induced stronger neovascular reaction in mice skin than did the sera of corresponding control people. Sera from both groups of people after neutralization with antihuman IL-18 antibodies lost substantial part of their angiogenic activity.

Diabetic retinopathy is one of the most common causes of blindness. The majority of studies concerning this problem were performed in patients with late stage of disease, demonstrating proliferative retinopathy, when malformations of retinal vessels became irreversible. Numerous angiogenic factors related to retinal angiogenesis have been described. Among them, VEGF is thought to be the major mediator of proliferative retinopathy. Our present study was performed on sera collected from patients with earlier stage of ocular complications, manifested as background retinopathy. We have believed that the knowledge of the earliest events leading to pathological angiogenesis may be valuable for establishing some prophylactic regimens. Sera of 22 persons with DM1, aged 33-70 years, 37 persons with DM2, aged 37-79 years, 51 healthy people, aged 22-80 years (as controls) were studied. Direct serum-induced cutaneous angiogenesis test in mice (SIA) was applied. VEGF concentration in sera was mesured by ELISA (R & D Systems) test. Angiogenic activity and VEGF concentration of DM1 patients sera were highly statistically lower than these parameters in DM2 patients and controls.

Galectin-3 is a 31 kDa member of a growing family of beta-galactoside-binding animal lectins. This protein is expressed in a variety of tissues and cell types and is mainly found in the cytoplasm, although, depending on cell type and proliferative state, a significant amount of this lectin can also be detected in the nucleus, on the cell surface or in the extracellular environment. Galectin-3 is secreted from cells by a novel and incompletely understood mechanism that is independent of the classical secretory pathway through the endoplasmic reticulum/Golgi network. Galectin-3 exhibits pleiotropic biological function, playing a key role in many physiological and pathological processes.

Diabetes is associated with a hypercoagulable state. Eighty percent of patients with diabetes mellitus die due to various thrombotic vascular complications. Disorder of coagulation and fibrynolysis is associated with diabetic retinopathy and nephropathy. Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells. Various serine proteases play important role in this process. The homeostatic system is also the source of endogenous inhibitors of angiogenesis. Human serum contains various factors able to induce or suppress formation of new blood vessels. The aim of the present study was to evaluate the activity of some angiogenesis inhibitors, anti-proteases, anti-thrombin III, a1 anti-trypsin and a2 anti-plasmin in sera of patients with diabetes mellitus type 1 and 2 and non-proliferative retinopathy, and to correlate this activity to total angiogenic potential of these sera, measured by mice cutaneous test. Sera of 22 persons with DM1, aged 33-70 years, 35 persons with DM2, aged 37-79 years, and 51 healthy people, aged 22-80 years (as control group) were studied. Direct serum-induced cutaneous angiogenesis test in mice (SIA) was applied. Berichrom (ade Behring) tests and immunoturbidimetric method were used for evaluation of anti-proteases activity. Angiogenic activity of DM1 patients sera was statistically lower than this parameter in DM2 patients and in control group. Levels of anti-proteases were similar in DM1, DM2 and control group, with one exception: anti-thrombin level was lower in DM2 patients' sera than this in the control group. Analysis of correlation revealed important difference in behaviour of DM1 sera, as compared to other groups. Significant negative correlation was observed between angiogenic activity and anti-thrombin, as well as anti-trypsin level of DM1 patients' sera. On the other hand, correlation analysis performed for the sera of control group revealed significant positive correlation between their angiogenic activity and anti-thrombin level. No other correlations were found.

The critical steps of modern cardiopulmonary resuscitation had arrived in the middle of our 20th century. Mouth-to-mouth ventilation was rediscovered and proven more effective than the manual methods and was combined with external chest compression into what we know today as cardiopulmonary resuscitation.