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Quality requirements and tests taken on the surfacing layer Inconel 625 are presented in the article. The reasons of using surfacing layer Inconel 625 and technologies of its making with a particular emphasis on the CMT method are described. Quality requirements for the surfacing weld Inconel 625 are provided. Basic requirements included in the Merkblatt 1166, as well as additional requirements, which are reflected in the technical specifications of the boilers’ producers are specified.

The relationships between shoot and root traits can inform plant selection for restoration, forestry, and agriculture and help to identify relationships that inform plant productivity and enhance their performance. But the strength of coordination between above- and belowground morphological and physiological traits varies due to differences in edaphic properties and population variation. More assessments are needed to determine what conditions influence these relationships. So, we tested whether plant population and soil texture affect the relationship between shoot and root traits which have important ecological ramifications for competition and resource capture: shoot height and root tip production. We grew seedlings of two populations of Bromus tectorum due to is fast growing nature in a growth chamber in loam soil, sand, and clay. We found variation in height by plant population and the substrate used (R2 = 0.44, p < 0.0001), and variation in root tip production by the substrate used (R2 = 0.33, p < 0.0001). Importantly, we found that relationships between shoot height and root tip production varied by soil texture and population (R2 = 0.54, p < 0.0001), and growth in sand produced the strongest relationship and was the most water deficient substrate (R2 = 0.32). This shows that screening populations under several environments influences appropriate plant selection.

Lipoma is a benign tumour originating from mature adipose tissue. It can occur in any place in the body where adipose tissue is located. Intraosseous lipoma is a very rare bone tumour. The authors present an infrequent case involving intraosseous lipoma of the mandible in a 32-year old man and provide a review of case studies documented earlier in the literature.

McCune Albright syndrome (MCA) is a rare complication of genetic origin. The authors present a case study of a patient with MCA diagnosed with multifocal fibrous dysplasia in his limb and craniofacial bones. The symptoms of the disease in the patient’s facial and oral tissue and the treatment administered have been described.

The development and widespread use of ICT in society are reflected by the way research is designed and conducted. The Computer Assisted Web Interview method is becoming more attractive and is a frequently used method in health sciences. The National Study of ICT Use in Primary Healthcare in Poland was conducted using this method. The aim of this paper is to present the major advantages and disadvantages of web surveys. Technical aspects of methodology and important stages of the aforementioned study, as well as key elements for its procedure, are mentioned. The authors also provide reflections based on their analysis of this national study, conducted between January and April 2014.

There are practical aspects of a quality control of the Inconel 625 surfacing weld in terms of undergone examinations and detected defects in chapter three of the article. Visual inspections, examinations of the thickness of the surfacing weld, examinations of an iron content on the surface of the surfacing weld and detecting surface cracks are described. A process of undergone practical examinations is presented.

Transmigration is a tooth pathology in which the migrating tooth bud passes the median plane. Methods: This study is a presentation of the diagnostic and therapeutic outcomes in the cases of 4 stomach teeth transmigrations diagnosed in 3 patients with mandibular retrognathia which was a complication after osteitis in the postnatal period and infancy. Results: Extending imaging diagnostics to include CT, most preferably CBCT, makes it possible to precisely evaluate a transmigrated canine’s position and to plan a course of treatment. Conclusions: Planning of the treatment of teeth in transmigration in patients with temporomandibular ankylosis should be done by a team consisting of an orthodontist and a surgeon.

Objective: Because free sample of prescription medications have been shown to influence prescribing habits of physicians, we sought to discern if promotional efforts of a retail pharmacy influenced prescriptions filled in our county after a free antibiotic program was initiated. Methods: Retrospective analysis of prescription antibiotics filled throughout the county was performed. Prescriptions filled during the first 6 months of the year before the program was initiated were compared to prescriptions filled during the first 6 months of the year immediately following initiation of the promotion. Results: A total of 436,372 antibiotic prescriptions were dispensed during that time. The number of antibiotics filled that were included in the promotion increased by 13.4% while the number of antibiotics filled that were excluded from the promotion decreased by 20.4%. Conclusion: These data suggest that the promotional pricing of the antibiotics had a significant impact on the number of prescriptions filled in each category. Because a prescription written does not always equate to a prescription filled, further investigation is needed to confirm the relationship between these promotions and actual prescriber habits.

Abstract Background Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.

Abstract Background Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES - Paediatric Asthma Gene Environment Study). Methods Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. Results To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV1 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. Conclusions It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

This paper presents an innovative approach to the integration of thermoelectric microgenerators (μTEGs) based on thick-film thermopiles of planar constantan-silver (CuNi-Ag) and calcium cobaltite oxide-silver (Ca 3 Co 4 O 9 -Ag) thick-film thermopiles with radio frequency identification (RFID) technology. The goal was to consider using the TEG for an active or semi-passive RFID tag. The proposed implementation would allow the communication distance to be increased or even operated without changing batteries. This article discusses the principles of planar thermoelectric microgenerators (μTEGs), focusing on their ability to convert the temperature difference into electrical energy. The concept of integration with active or semi-passive tags is presented, as well as the results of energy efficiency tests, considering various environmental conditions. On the basis of the measurements, the parameters of thermopiles consisting of more thermocouples were simulated to provide the required voltage and power for cooperation with RFID tags. The conclusions of the research indicate promising prospects for the integration of planar thermoelectric microgenerators with RFID technology, opening the way to more sustainable and efficient monitoring and identification systems. Our work provides the theoretical basis and practical experimental data for the further development and implementation of this innovative technology.

Background: We are currently experiencing a third digital revolution driven by artificial intelligence (AI), and the emergence of new chat generative pre-trained transformer (ChatGPT) represents a significant technological advancement with profound implications for global society, especially in the field of education., Methods: The aim of this study was to see how well ChatGPT performed on medical school exams and to highlight how it might change medical education and practice. Recently, OpenAI's ChatGPT (OpenAI, San Francisco; GPT-4 May 24 Version) was put to the test against a significant Polish medical specialization licensing exam (PES), and the results are in. The version of ChatGPT-4 used in this study was the most up-to-date model at the time of publication (GPT-4). ChatGPT answered questions from June 28, 2023, to June 30, 2023., Results: ChatGPT demonstrates notable advancements in natural language processing models on the tasks of medical question answering. In June 2023, the performance of ChatGPT was assessed based on its ability to answer a set of 120 questions, where it achieved a correct response rate of 67.1%, accurately responding to 80 questions., Conclusions: ChatGPT may be used as an assistance tool in medical education. While ChatGPT can serve as a valuable tool in medical education, it cannot fully replace human expertise and knowledge due to its inherent limitations.

Hypercholesterolemia affects the neurovascular unit, including the cerebral blood vessel endothelium. Operation of this system, especially in the context of energy metabolism, is controlled by extracellular concentration of purines, regulated by ecto-enzymes, such as e-NTPDase-1/CD39, ecto-5'-NT/CD73, and eADA. We hypothesize that hypercholesterolemia, via modulation of the activity of nucleotide metabolism-regulating ecto-enzymes, deteriorates glycolytic efficiency and energy metabolism of endothelial cells, which may potentially contribute to development of neurodegenerative processes. We aimed to determine the effect of hypercholesterolemia on the concentration of purine nucleotides, glycolytic activity, and activity of ecto-enzymes in the murine brain microvascular endothelial cells (mBMECs). We used 3-month-old male LDLR -/- /Apo E -/- double knockout mice to model hypercholesterolemia and atherosclerosis. The age-matched wild-type C57/BL6 mice were a control group. The intracellular concentration of ATP and NAD and extracellular activity of the ecto-enzymes were measured by HPLC. The glycolytic function of mBMECs was assessed by means of the extracellular acidification rate (ECAR) using the glycolysis stress test. The results showed an increased activity of ecto-5'-NT and eADA in mBMECs of the hypercholesterolemic mice, but no differences in intracellular concentration of ATP, NAD, and ECAR between the hypercholesterolemic and control groups. The changed activity of ecto-5'-NT and eADA leads to increased purine nucleotides turnover and a shift in their concentration balance towards adenosine and inosine in the extracellular space. However, no changes in the energetic metabolism of the mBMECs are reported. Our results confirm the influence of hypercholesterolemia on regulation of purine nucleotides metabolism, which may impair the function of the cerebral vascular endothelium. The effect of hypercholesterolemia on the murine brain microvascular endothelial cells (mBMECs). An increased activity of ecto-5'-NT and eADA in mBMECs of the LDLR -/- /Apo E -/- mice leads to a shift in the concentration balance towards adenosine and inosine in the extracellular space with no differences in intracellular concentration of ATP. Figure was created with Biorender.com., (© 2023. The Author(s).)

Over recent years, the global healthcare system has experienced a notable increase in the prevalence of obesity and its associated health complications such as hypertension, type 2 diabetes, lipid disorders, etc. What is more, one of the significant phenomena is the increasing demand for bariatric procedures among individuals of working age due to the high prevalence of type III obesity and type II obesity with co-morbidities. This trend is pronounced in Poland, due to the increasing number of patients meeting the qualifying criteria for surgery among professionally active and inactive patients. The aim of this study is to characterize the alarmingly high number of candidates for bariatric procedures among professionally active Poles. In total, the results of 2,056,861 initial, control, and periodic visits as part of the occupational medicine certificate were analyzed-collected from 1,342,749 unique patients (51.7% men; mean age of whole group: 36.81, SD = 10.91). Statistical calculations were performed, qualitative data were assessed using percentage and occurrence counts, while qualitative data were described using mean (M), standard deviation (SD), median, skewness, kurtosis, and range values. Results with p < 0.05 were deemed significant. Chi-square analysis and one-way ANOVA (with Scheffe's post hoc test) were employed. Charts were created in the R program. It was noticed that there was a consistent rise in the proportion of individuals classified as candidates for bariatric procedures (an increase of 0.3%) alongside a notable decrease in the percentage of individuals maintaining a healthy body weight. Moreover, it is imperative to conduct yearly evaluations of the prevalence of obesity and its associated health conditions. It should be noted that hypertension occurred in 42.2% of patients, type 2 diabetes in 6.2% of patients, and lipid disorders in 8.4% of patients with third-degree obesity. This proactive approach is essential in order to adequately equip the healthcare system to address the increasing population of obese individuals, especially candidates for bariatric procedures.

The aim of this study was to assess the association of long-term exposure to particulate matter with aerodynamic diameter, PM2.5, PM10, NO 2 and SO 2 as well as CO, with lung adenocarcinoma (AD) in south-east Poland for the years from 2004 to 2014. The study group consisted of 4296 patients with lung adenocarcinoma and the level of selected pollutants. To analyse the data, a standard statistics for cohort data, that is a risk ratio (RR), was used. The dependencies occurring in the distribution of pollutants and cancer incidence were examined using Moran's I correlation coefficient. The current study suggests that PM10, NO 2 and SO 2 exposure as an air pollutant may increase female lung adenocarcinoma incidence. In men, the increased risk of adenocarcinoma lung cancer is affected by SO 2 and PM10. A high morbidity rate in urban areas and suburbs may be connected with commuting from moderately polluted living areas to highly polluted working areas.

Over the past few years, artificial intelligence (AI) has significantly improved healthcare. Once the stuff of science fiction, AI is now widely used, even in our daily lives - often without us thinking about it. All healthcare professionals - especially executives and medical doctors - need to understand the capabilities of advanced AI tools and other breakthrough innovations. This understanding will allow them to recognize opportunities and threats emerging technologies can bring to their organizations. We hope to contribute to a meaningful public discussion about the role of this new type of AI and how our approach to healthcare and medicine can best evolve with the rapid development of this technology. Since medicine learns by example, only a few possible uses of AI in medicine are provided, which merely outline the system's capabilities. Among the examples, it is worth highlighting the roles of AI in medical notes, education, preventive programs, consultation, triage and intervention. It is believed by the authors that large language models such as chat generative pre-trained transformer (ChatGPT) are reaching a level of maturity that will soon impact clinical medicine as a whole and improve the delivery of individualized, compassionate, and scalable healthcare. It is unlikely that AI will replace physicians in the near future. The human aspects of care, including empathy, compassion, critical thinking, and complex decision-making, are invaluable in providing holistic patient care beyond diagnosis and treatment decisions. The GPT-4 has many limitations and cannot replace direct contact between an experienced physician and a patient for even the most seemingly simple consultations, not to mention the ethical and legal aspects of responsibility for diagnosis.

The development of medicine is based not only on the introduction of new methods of treatment, but also on the use of increasingly effective drugs, including antithrombotic drugs. Drugs that inhibit the activity of platelets (antiplatelet and anti-aggregating drugs) and pharmaceuticals that inhibit the activity of plasma coagulation factors (anticoagulants) are used in antithrombotic therapy. In our daily practice we encounter patients who take chronic antiplatelet or anticoagulant drugs. However, more and more often we are dealing with patients who are treated with two antiplatelet drugs, an antiplatelet and an anticoagulant or even undergoing triple antithrombotic therapy. When preparing the patient for invasive craniofacial procedures, it should be assessed whether the temporary discontinuation of antithrombotic treatment due to the fear of excessive perioperative bleeding is justified and will not result in life-threatening thromboembolic complications. The authors discuss in detail the medications used in modern antithrombotic treatment and present a perioperative management procedure with a patient who takes l4 z of these medications chronically.

Piptoporus betulinus is a fungus known for its medicinal properties. It possesses antimicrobial, anti-inflammatory, and anti-cancer activity. In this study, several tests were performed to evaluate the cytotoxic effect of the ethanolic extract of Piptoporus betulinus on two melanoma human cell lines, WM115 primary and A375 metastatic cell lines, as well as Hs27 human skin fibroblasts. The extract proved to affect cancer cells in a dose-dependent manner, and at the same time showed a low cytotoxicity towards the normal cells. The total phenolic content (TPC) was determined spectrophotometrically by the Folin-Ciocalteu method (F-C), and the potential antioxidant activity was measured by ferric-reducing antioxidant power (FRAP) assay. One of the active compounds in the extract is betulin. It was isolated and then its cytotoxic activity was compared to the results obtained from the Piptoporus betulinus extract. To further understand the mechanism of action of the extract's anticancer activity, tests on model cell membranes were conducted. A model membrane of a melanoma cell was designed and consisted of 1,2-dimyristoyl-sn-glycero-3-phosphocholine, disialoganglioside-GD 1a and cholesterol: DMPC:GD 1a :chol (5:2:3 mole ratio). Changes in a Langmuir monolayer were observed and described based on Π - A mol isotherm and compressibility modulus changes. LB lipid bilayers were deposited on a hydrophilic gold substrate and analyzed by IR and X-ray photoelectron spectroscopy. Our study provides new data on the effect of Piptoporus betulinus extract on melanoma cells and its impact on the model of melanoma plasma membranes.

The pandemic declared in many countries in 2020 due to COVID-19 led to the freezing of economies and the introduction of distance learning in both schools and universities. This unusual situation has affected the mental state of citizens, which has the potential to lead to the development of post-traumatic stress and depression. This study aimed to assess the level of stress in dental students in the context of the outbreak of the SARS-CoV-2 virus pandemic. A survey on the PSS-10 scale was prepared to measure the level of perceived stress. The study included 164 dental students at the Faculty of Medical Sciences of the Medical University of Silesia in Katowice, Poland. The results showed the impact of COVID-19 on the stress of students, with 67.7% reporting high levels of stress. The study also revealed that stress was higher among older female students. This paper recommends that the university provide more intensive psychological care as psychological first aid strategies in epidemics or natural disasters and to consider telemedicine in order to deliver services due to the limitations of the pandemic.

Background: Dental schools are considered to be a very stressful environment; the stress levels of dental students are higher than those of the general population. The aim of this study was to assess the level of stress among dental students while performing specific dental procedures., Methods: A survey was conducted among 257 participants. We used an original questionnaire, which consisted of 14 questions assigned to three categories: I-Diagnosis, II-Caries Treatment, and III-Endodontic Treatment. Each participant marked their perceived level of stress during the performed dental treatment procedures. The scale included values of 0-6, where 0 indicates no stress, while 6 indicates high stress., Results: Third- (p=0.006) and fourth-year (p=0.009) women were characterized by a higher level of perceived stress during dental procedures related to caries treatment. Caries treatment procedures were the most stressful for 18.3% of third-year students, 4.3% of fourth-year students, and 3.2% of fifth-year students. Furthermore, 63.4% of third-year students, 47.3% of fourth-year students, and 17.2% of fifth-year students indicated that they felt a high level of stress when performing endodontic procedures., Conclusion: Third- and fourth-year female students are characterized by a higher level of stress during caries and endodontic treatment procedures. The most stressful treatments for participants were endodontic treatment procedures.

Adequate ehealth literacy is one of the key instruments safeguarding people against unreliable health-related information obtained from the Internet. This paper presents an assessment of the reliability and the validity of a Polish version of the ehealth literacy scale (Pl-eHEALS). The assessment was carried out on the basis of two nationally representative samples of the Polish population. In the first survey of adults at least 50 years old, the technique of computer-assisted telephone interviewing (CATI) was applied. In the second survey of young adult women (18-35 years old), the technique of computer-assisted web interviewing (CAWI) was used. The reliability and the validity of the Pl-eHEALS was analyzed. There were no floor or ceiling effects revealed in either sample. The Cronbach's alpha coefficients were 0.90 and 0.88, and Guttman split-half coefficients were 0.89 and 0.81, respectively. Exploratory factors analysis revealed single factor models in both cases. The sum of squared loadings in the first survey was 6.090 and accounted for 58.72% of the variance. In the second survey, the sum was 5.927 and was responsible for 55.06% of the variance. Hypothesis testing showed that, for older adults, higher ehealth literacy was prevalent in the respondents who used the Internet more frequently. Among young adult women, higher readiness to use the Internet as a primary source of health-related information and to undertake specific internet health-related activities was associated with higher ehealth literacy. The analysis reported in this paper confirmed the reliability and the validity of the instrument. It should be stressed that, prior to this study, there was no validated Polish version of the eHEALS that could be used with Polish-speaking respondents.

Aim of the Study: The objective of the study was to analyse the survival rate of women with malignant ovarian tumours in the years 1990-2015 in the Podkarpacie province., Material and Methods: The database used for calculations covered 2399 cancer incidences verified at the end of 2014. The estimated relative survival rates were calculated by means of the Hakulinen method., Results: The number of recorded cases amounted to 196 in 2015 and was higher by 86.7% than in 1990. The rates of one-year, three-year, and five-year survival was 72.5%, 51.2%, and 42.4%, respectively., Conclusions: Survival rates of women with ovarian cancer in the Podkarpacie province are comparable to survivals calculated for the entire Poland region. Despite the low risk factor, women suffering from ovarian adenocarcinoma have lower survival rates than others, and as many as 42.5% of patients with adenocarcinoma were diagnosed in stage IV. Steps aimed at improvement of detectability of ovarian cancers in the earliest possible stage should be taken. This should increase survival rates in each age group., Competing Interests: The authors declare no conflict of interest.

The incidence of malignant melanoma, the most aggressive skin cancer, is increasing constantly. Despite new targeted therapies, the prognosis for patients with metastatic disease remains poor. Thus, there is a need for new combinational treatments, and antineoplastic agents potentially valuable in this approach are inhibitors of the ubiquitin-proteasome system (UPS). In this work, we analyze the cytotoxicity mechanisms of proteasome inhibitors (MG-132, epoxomicin, and lactacystin) in a specific form of melanoma which does not synthesize melanin-the amelanotic melanoma (Ab cells). We found that the most cytotoxic of the compounds tested was epoxomicin. Caspase-9 activation as well as cytochrome C and AIF release from mitochondria indicated that exposure to epoxomicin induced the mitochondrial pathway of apoptosis. Epoxomicin treatment also resulted in accumulation of Bcl-2 family members-proapoptotic Noxa and antiapoptotic Mcl-1, which were postulated as the targets for bortezomib in melanoma. Inhibition of caspases by BAF revealed that cell death was partially caspase-independent. We observed no cell cycle arrest preceding the apoptosis of Ab cells, even though cdk inhibitors p21 Cip1/Waf1 and p27 Kip1 were up-regulated. The cell cycle was blocked only after inactivation of caspases by the pan-caspase inhibitor BAF. In summary, this is the first study exploring molecular mechanisms of cell death induced by epoxomicin in melanoma. We found that Ab cells died on the mitochondrial pathway of apoptosis and also partially by the caspase-independent way of death. Apoptosis induction was fast and efficient and was not preceded by cell cycle arrest.

The broad variety of substances that inhibit the action of the ubiquitin-proteasome system (UPS)-known as proteasome inhibitors-have been used extensively in previous studies, and they are currently frequently proposed as a novel form of cancer treatment and as a protective factor in intracerebral hemorrhage treatment. The experimental data on the safest route of proteasome inhibitor administration, their associated side effects, and the possible ways of minimizing these effects have recently become a very important topic. The aim of our present study was to determine the effects of administering of MG-132, lactacystin and epoxomicin, compounds belonging to three different classes of proteasome inhibitors, on the ependymal walls of the lateral ventricle. Observations were made 2 and 8 weeks after the intraventricular administration of the studied substances dissolved in dimethyl sulfoxide (DMSO) into the lateral ventricle of adult Wistar rats. Qualitative and quantitative analysis of brain sections stained with histochemical and inmmunofluorescence techniques showed that the administration of proteasome inhibitors caused a partial occlusion of the injected ventricle in all of the studied animals. The occlusion was due to ependymal cells damage and subsequent ependymal discontinuity, which caused direct contact between the striatum and the lateral nuclei of the septum, mononuclear cell infiltration and the formation of a glial scar between these structures (with the activation of astroglia, microglia and oligodendroglia). Morphologically, the ubiquitin-positive aggregates corresponded to aggresomes, indicating impaired activity of the UPS and the accumulation and aggregation of ubiquitinated proteins that coincided with the occurrence of glial scars. The most significant changes were observed in the wall covering the striatum in animals that were administered epoxomicin, and milder changes were observed in animals administered lactacystin and MG-132. Interestingly, DMSO administration also caused damage to some of the ependymal cells, but the aggresome-like structures were not formed. Our results indicate that all of the studied classes of proteasome inhibitors are detrimental to ependymal cells to some extent, and may cause severe changes in the ventricular system. The safety implications of their usage in therapeutic strategies to attenuate intracerebral hemorrhagic injury and in brain cancer treatment will require further studies.

The proteins' ubiquitination and their further degradation by proteasomes are crucial for cell cycle regulation, transcription and DNA replication, inflammatory response, and apoptosis. Proteasome inhibitors have recently become considered as a promising method in cancer and inflammatory disease therapy. In this study, utilizing the rat model, we try to establish the influence of proteasome inhibitor MG-132: (1) on the basis of spontaneous and evoked locomotor activity and (2) on the condition of nigrostriatal projections eight weeks after MG-132 intraperitoneal administration. We also discuss the current status of knowledge about intraperitoneal administration of MG-132, a laboratory method that is being used more and more. Our results revealed a lack of motor abnormalities, but significant loss (20%) of substantia nigra pars compacta dopaminergic neurons after systemic MG-132 administration. This loss was accompanied by a corresponding decrease (8%) of density of dopaminergic terminals in dorsolateral striatum. Moreover, evidence of very limited but ongoing fibre degeneration within the dorsal striatum suggests that MG-132 severely disturbed the nigrostriatal pathway. In summary, intraperitoneal application of proteasome inhibitor MG-132, despite the encouraging results of experimental treatment and prevention of many pathological processes, should be used with caution because of the potential adverse effects on the structure of the central nervous system, especially elements of the nigrostriatal pathway.

Calbindin-D28k (CB), parvalbumin (PV) and calretinin (CR) are calcium-binding proteins (CaBPs) considered to be markers for certain subpopulations of neurons in the central nervous system. The aim of this study was to describe the pattern of distribution of CB-, PV- and CR-immunoreactive elements in the rabbit corticomedial amygdaloid complex during the postnatal period. The time course of changes in CaBPs expression during maturation of the selected nuclei indicates their diversity. During the first month after birth, CaBPs expression stabilizes earliest in the anterior cortical and then in the medial nuclei. Later, during the second month of postnatal life, the posteromedial and posterolateral cortical nuclei maturate. The central nucleus requires a considerably longer time to reach maturity - about three months are needed to stabilize CaBPs expression in all its subdivisions. This nucleus also shows the most differentiated, time-dependent distribution of CaBPs immunoreactivity (especially CB), distinct in its divisions. The differences in the CaBPs immunoreactivity confirm previous reports concerning dissimilar origin and development, and also reflect the diversity of connectivity of the amygdaloid body - the collection of nuclei, considered as one functional integrity.

Reactive astrogliosis is regarded as an universal astrocytic response to different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP) up-regulation, cellular hypertrophy and proliferation. The origin of reactive and proliferating cells in the adult brain is still disputable. Persistent progenitors as well as de-differentiating adult cells of various glial lineages are regarded as possible candidates. Pax6 transcription factor is one of the characteristic markers of astroglial de-differentiation, also important for regulation of neural and glial proliferation. Various kinds of pathological stimuli evoke reactive response, differentiated in its morphological, biochemical and immunological character. The aim of this study was to assess the dynamics of astroglial morphological and proliferative response to ischemic injury. One-hour transient focal cerebral ischemia was applied to evoke the reactive astrogliosis in twenty five adult male Wistar rats. The astrocytic morphological and proliferative reactions to ischemia were studied in the period of 6 weeks by means of GFAP and Pax6 immunofluorescent staining. A strong reactive astroglial response was observed in the cerebral cortex and striatum, manifested by GFAP and Pax6 up-regulation and astrocytic hypertrophy. Apparent morphological changes appeared within 24 hrs after ischemia. The GFAP/Pax6 colocalization was numerous and observed 24 hrs after ischemia. A characteristic spatial distribution of GFAP/Pax6 double-labelled astrocytes and Pax6 single-labelled nuclei was revealed, with the latter situated more distantly from the ischemic core. The maximal intensity of astrocytic reaction was present from the first post-ischemic week. Astroglial hypertrophic changes and proliferative reaction were more intense in the striatum than in the cerebral cortex. Our observations reveal intensive astroglial de-differentiation and proliferative response, reflected by dynamic Pax6 up-regulation within GFAP-immunoreactive astrocytes. Transient cerebral ischemia evokes strong reactive astrogliosis, which is apparently differentiated in respect to the post-ischemic period and particular brain structure.

Under favorable conditions of pH and temperature, poly(L-glutamic acid) (PLGA) adopts different types of secondary and quaternary structures, which include spiral assemblies of amyloid-like fibrils. Heating of acidified solutions of PLGA (or PDGA) triggers formation of β(2)-type aggregates with morphological and tinctorial properties typical for amyloid fibrils. In contrast to regular antiparallel β-sheet (β(1)), the amide I' vibrational band of β(2)-fibrils is unusually red-shifted below 1600 cm(-1), which has been attributed to bifurcated hydrogen bonds coupling C═O and N-D groups of the main chains to glutamic acid side chains. However, unlike for pure PLGA, the amide I' band of aggregates precipitating from racemic mixtures of PLGA and PDGA (β(1)) is dominated by components at 1613 and 1685 cm(-1)-typically associated with intermolecular antiparallel β-sheets. The coaggregation of PLGA and PDGA chains is slower and biphasic and leads to less-structured assemblies of fibrils, which is reflected in scanning electron microscopy images, sedimentation properties, and fluorescence intensity after staining with thioflavin T. The β(1)-type aggregates are metastable, and they slowly convert to fibrils with the infrared characteristics of β(2)-type fibrils. The process is dramatically accelerated under high pressure. This implies the presence of void volumes within structural defects in racemic aggregates, preventing the precise alignment of main and side chains necessary to zip up ladders of bifurcated hydrogen bonds. As thermodynamic costs associated with maintaining void volumes within the racemic aggregate increase under high pressure, a hyperbaric treatment of misaligned chains leads to rectifying the packing defects and formation of the more compact form of fibrils.

Amyloid fibrils, which are often associated with certain degenerative disorders, reveal a number of intriguing spectral properties. However, the relationship between the structure of fibrils and their optical traits remains poorly understood. Poly(L-glutamic) acid is a model polypeptide shown recently to form amyloid-like fibrils with an atypical infrared amide I' band at 1595 cm(-1), which has been attributed to the presence of bifurcated hydrogen bonds coupling C═O and N-D groups of the main chains to glutamate side chains. Here we show that this unusual amide I' band is observed only for fibrils grown from pure enantiomers of the polypeptide, whereas fibrils precipitating from equimolar mixtures of poly(L-glutamic) and poly(D-glutamic) acids have amide I' bands at 1684 and 1612 cm(-1), which are indicative of a typical intermolecular antiparallel β-sheet. Pure enantiomers of polyglutamic acid form spirally twisted superstructures whose handedness is correlated to the amino acid chirality, while fibrils prepared from the racemate do not form scanning electron microscopy (SEM)-detectable mesoscopically ordered structures. Vibrational circular dichroism (VCD) spectra of β-aggregates prepared from mixtures of all L- or D-polyglutamic acid in varying ratios indicate that the enhancement of VCD intensity correlates with the presence of the twisted superstructures. Our results demonstrate that both IR absorption and enhanced VCD are sensitive to subtle packing defects taking place within the compact structure of amyloid fibrils.

Preferential atrophy of Type-II muscle fibres occurs in several clinical situations, including cachexia, muscle disuse, chronic glucocorticoid treatment, remote neoplasia, and sometimes as an aspect of recent-denervation. For the patient, the Type-II atrophy itself might be unfavourable (as a glucocorticoid side-effect) or favourable (survivalistic via the muscle-alanine liver-gluconeogenesis pathway in starvation). The cellular mechanisms underlying Type-II fibre atrophy are unclear. Myostatin (Mstn) is physiologically a negative regulator of muscle mass and strength. In this study we evaluated a possible role of Mstn in Type-II fibre atrophy in human muscle. Mstn and Mstn precursor protein (MstnPP) were studied in 10-muscle biopsies containing Type-II fibre atrophy and in 17 disease and normal control muscle biopsies. When comparison was made with normal control fibres, we found the following: 1) by immunocytochemistry, diffusely increased Mstn/MstnPP in the atrophic Type-II muscle fibres; 2) by immunoblots, Mstn/MstnPP increased individually; 3) by RT-PCR, no increase in MstnPP mRNA. In conclusion, our results a) suggest that Mstn/ /MstnPP might play a role in the pathogenic cascade of Type-II muscle fibre atrophy; b) broaden our previously-described associations of Mstn in human muscle pathology, and c) could possibly lead to clinical prevention when Type-II muscle fibre atrophy is unfavourable, for instance in glucocorticoid therapy.

The piriform cortex (PC), the primary olfactory cortex, is involved in the processes of learning and stress response and possibly plays an important role in epileptogenic activity. The results of several recent studies suggest that those PC neurons that contain neuronal nitric oxide synthase (nNOS) may play a key role during spatial learning and in the modulation of initiation, propagation and generalisation of seizures in various experimental models and may influence neuronal vulnerability after epileptic insults. The aim of this study was to characterise the pattern of distribution and morphology of nNOS-immunoreactive elements in PC of the adult rabbit. The co-localisation of nNOS and calretinin (CR) was also studied. The pattern of nNOS-ir within the rabbit PC is similar to that described previously in other mammals. The morphology of nNOS-ir elements, namely varicose fibres and Cajal-Retzius cells, suggest that NO has an important influence on PC function. Surprisingly, in the rabbit PC nNOS-ir elements show a very low level of co-localisation with CR-ir.

The posterior thoracic wall, an area drained by the azygos venous system, is a common site for surgical intervention. Since the venous part of the cardiovascular system is subject to most common variation, abnormalities in the azygos venous system are often reported. Some of the anatomical variants have significant clinical implications for computed tomography image assessment and mediastinal surgery. During dissection of the posterior mediastinum in a 76 year-old Caucasian male cadaver we found a rare variation in the azygos venous system. The hemiazygos vein drained the left 9th to 11th left posterior intercostal veins. While passing ventrally to the aorta at the level of the body of the eighth thoracic vertebra it was joined by two separate vessels found to be the continuations of the 7th and 8th left posterior intercostal veins. The resultant dilated vessel, termed the "interazygos vein", then opened into the azygos vein on the right side of the vertebral column. Variation in the azygos venous system has often been reported, but the abnormality observed by us appears to be extremely rare. The interazygos vein passing ventrally to the aorta may mimic enlarged lymph nodes and cause misinterpretation of a computed tomography image or, if accidentally damaged during mediastinal surgery, may lead to intraoperative haemorrhage. To the best of our knowledge this report provides new data of potential clinical significance.

Claustrum is a telencephalic structure integrating information of various modalities. Proper functioning of this structure depends on the presence of a network of intrinsic connections. This includes GABA-ergic neuronal populations that also contain calcium-binding proteins (CaBPs). The goal of this study was to analyze qualitative and quantitative the 5-HT-containing fibers in the rat claustrum and to assess the relationships between these fibers and the populations of claustral neurons expressing CaBPs. We used the methods of immunocytochemistry and morphometry. The serotonergic fibers in the claustrum are heterogeneous, both with respect to their morphology and spatial distribution. Thin varicose fibers are more numerous and are homogeneously distributed within the claustrum. Remaining fibers were thicker and possessed larger varicosities. They were present mainly in the ventral part of the claustrum. Although the serotonergic fibers are found in the vicinity of claustral cells containing CaBPs, direct contacts between these fibers and cells are rare. Other mechanisms, including volume transmission, may possibly mediate serotonergic influences.

The glial cells play an important role in pathophysiology of the intracerebral haemorrhage (ICH). Thus the attempt at evaluating the possible influence of the propofol on the reactivity of astro- and microglial cells in the course of ICH was performed. 50 rats were divided into two groups depending on the applied anaesthesia. All animals were generally anaesthetized with fentanyl, dehydrobenzperidol and midazolam. No additional agents were given to the animals of the control group (group I). In the experimental group (group II), the animals received additionally intraperitoneally propofol in a dose of 50 mg/kg every thirty minutes. ICH was produced through infusion of the blood into the striatum. The astrocytic and microglial cells population was assessed on the 1, 3, 7, 14 and 21 days after producing a haematoma using antibodies anti-GFAP and OX42. The stereological analysis was applied to estimate the numerical density of immunoreactive cells and the distribution of their types. On the 14th and 21st days of observation the density of GFAP-immunoreactivity (ir) cells was significantly higher in group II than that in group I. There were no differences in percentage distribution of GFAP-ir astrocytes between group I and group II. On the 3rd, 14th and 21st days of observation the density of OX42-ir cells was higher in group II in comparison with group I. For the 7th, and 21st days of survival the percentage of the ameboid form of OX42-ir cells was significantly lower in group I than that in group II. The administration of propofol during anaesthesia in the animals with ICH has evoked an increase of the activation of the astro- and microglial cells.

Intracerebral haematoma was produced in 25 adult rats by infusion of 100 microl of autologous blood into the striatum. The animals' brains were removed at 1, 3, 7, 14 and 21 days after production of the haematoma. The TUNEL method was used to detect DNA fragmentation and TUNEL-positive cells were qualified. TUNEL-positive cells were already found on the first day of observation and were present for three weeks after haematoma production. These results provide evidence that programmed cell death is associated with intracerebral haemorrhage.

40 adult Wistar rats were divided into two groups depending on the applied anaesthesia. In both groups animals were generally anaesthetized with fentanyl, dehydrobenzperidol administered intraperitoneally and midazolam given intramuscularly. In the second group (SEVO) animals received sevoflurane of 2.2 vol% end-tidal concentration. Intracerebral haematoma was produced through infusion of 100 microl of autologous blood into the striatum. Each group was divided into five subgroups depending on the length of survival period: 1, 3, 7, 14, 21 days. The astrocytic population was studied by means of anti-GFAP staining. Stereological analysis was applied to estimate the numerical density of immunoreactive cells and the distribution of their types. On 7th day of observation the density of GFAP-immunoreactive astrocytes in SEVO was lower (p<0,05) than that in the control group. In the control group, the increase (p<0.05) of per cent of activated astrocytes between the 1st and 3rd survival day was noted, which remained at this level till the end of observation. In SEVO group, the increase (p<0.05) of per cent of activated astrocytes between the 3rd and 7th day and the decrease (p<0.05) between the 14th and 21st survival day were observed. During days of observation the per cent of activated astrocytes was lower (p<0.05) in the SEVO group than that in the control group. Administration of sevoflurane during anaesthesia to animals with intracerebral haemorrhage has evoked not only the delay of the activation of astrocytes but also decrease in its level.