Effects of Piptoporus betulinus Ethanolic Extract on the Proliferation and Viability of Melanoma Cells and Models of Their Cell Membranes.

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-GD1a and cholesterol: DMPC:GD1a:chol (5:2:3 mole ratio). Changes in a Langmuir monolayer were observed and described based on Π-Amol 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.

Integration of value and action in medial prefrontal neural systems.

The rodent medial prefrontal cortex (mPFC) plays a key role in regulating cognition, emotion, and behavior. mPFC neurons are activated in diverse experimental paradigms, raising the questions of whether there are specific task elements or dimensions encoded by mPFC neurons, and whether these encoded parameters are selective to neurons in particular mPFC subregions or networks. Here, we consider the role of mPFC neurons in processing appetitive and aversive cues, outcomes, and related behaviors. mPFC neurons are strongly activated in tasks probing value and outcome-associated actions, but these responses vary across experimental paradigms. Can we identify specific categories of responses (e.g., positive or negative value), or do mPFC neurons exhibit response properties that are too heterogeneous/complex to cluster into distinct conceptual groups? Based on a review of relevant studies, we consider what has been done and what needs to be further explored in order to address these questions.

Purine tautomeric preferences and bond-length alternation in relation with protonation-deprotonation and alkali metal cationization.

Quantum chemical calculations were carried out for deprotonated (P-) and protonated purine (PH+) and for adducts with one alkali metal cation (P-M+ and PM+, where M+ is Li+ or Na+) in the gas phase {B3LYP/6-311+G(d,p)}, a model of perfectly apolar environment, and for selected structures in aqueous solution {PCM(water)//B3LYP/6-311+G(d,p)}, a reference polar medium for biological studies. All potential isomers of purine derivatives were considered, the favored structures indicated, and the preferred sites for protonation/deprotonation and cationization reactions determined. Proton and metal cation basicities of purine in the gas phase were discussed and compared with those of imidazole and pyrimidine. Bond-length alternations in the P, PH+, P-M+, and PM+ forms were quantitatively measured using the harmonic oscillator model of electron delocalization (HOMED) indices and compared with those for P. Variations of the HOMED values when proceeding from the purine structural building blocks, pyrimidine and imidazole, to the bicyclic purine system were also examined. Generally, the isolated NH isomers exhibit a strongly delocalized π-system (HOMED > 0.8). Deprotonation slightly increases the HOMED values, whereas protonation and cationization change the HOMED indices in different way. For bidentate M+-adducts, the HOMED values are larger than 0.9 like for the largely delocalized P-. The HOMED values correlate well in a comprehensive relationship with the relative Gibbs energies (ΔG) calculated for individual isomers whatever the purine form is, neutral, protonated, or cationized. When PCM-DFT model was utilized for P-, PH+, PM+, and P-M+ (M+ = Li+) both electron delocalization and relative stability are different from those for the molecules in vacuo. The solvation effects cause a slight increase in HOMEDs, whereas the ΔEs decrease, but in different ways. Hence, contribution of particular isomers in the isomeric mixtures of PH+, PM+, and P-M+ also varies. HOMED variations for the favored neutral, deprotonated, protonated, and lithiated forms of purine in the gas phase and aqueous solution.

Variations of the tautomeric preferences and π-electron delocalization for the neutral and redox forms of purine when proceeding from the gas phase (DFT) to water (PCM).

Quantum-chemical calculations were performed for all possible nine neutral tautomers of purine and their oxidized and reduced forms in water {PCM//DFT(B3LYP)/6-311+G(d,p)} and compared to those in the gas phase {DFT(B3LYP)/6-311+G(d,p)}. PCM hydration influences geometries, π-electron delocalization, and relative energies of purine tautomers in different ways. Generally, the harmonic oscillator model of electron delocalization (HOMED) indices increase when proceeding from the gas phase to aequeous solution for the neutral and redox forms of purine. Their changes for the neutral and oxidized tautomers are almost parallel to the relative energies showing that aromaticity plays an important role in the tautomeric preferences. Tautomeric stabilities and tautomeric preferences vary when proceeding from the gas phase to water indicating additionally that intra- and intermolecular interactions affect tautomeric equilibria. The tautomeric mixture of neutral purine in the gas phase consists mainly of the N9H tautomer, whereas two tautomers (N9H and N7H) dominate in water. For oxidized purine, N9H is favored in the gas phase, whereas N1H in water. A gain of one electron dramatically changes the relative stabilities of the CH and NH tautomers that C6H and C8H dominate in the tautomeric mixture in the gas phase, whereas N3H in water. These variations show exceptional sensitivity of the tautomeric purine system on environment in the electron-transfer reactions.

[Diagnostic problems with long QT syndrome in 5-year-old boy]. / Trudnosci diagnostyczne w rozpoznaniu zespolu wydluzonego QT u 5-letniego chlopca.

The authors described the case of 5-year-old boy, in whom a proper diagnosis was established after 19 months. In differential diagnosis, epileptic, tetanic and conversion seizures were taken into consideration.

[The pharmacological treatment of abulic posttraumatic state in children-preliminary report]. / Leczenie farmakologiczne pourazowego stanu abulicznego u dzieci--doniesienie wstepne.

UNLABELLED: The aim of the study was the evaluation of clinical condition of the children treated by Gliatilin and Dexamin for posttraumatic abulic state. MATERIAL AND METHOD: The study included 12 children (8 boys, 4 girls) at the age range between 7-16 years (mean age 7.8 years). The evaluation of clinical condition was performed on admission to the Department, and then at 3rd, 6th and 12th month after head injury. The authors analyzed the kind of injury (posttraumatic changes in neuroimaging) and evolution of patients' clinical condition in the follow-up. RESULTS: The most commonly observed reasons of trauma were motor vehicle accidents. The kind of pathology found on the base of neuroimaging did not affect the results of treatment. The patients were treated by Gliatilin, Dexamin or both. In spite of this treatment all children were rehabilitated and their hearing, sight and speech organ were stimulated. Six months after injury only one patient still presented abulic state and six of our patients were in good general condition. None of our patients revealed abulic state after 12 months of head trauma. In two children the Dexamin treatment was given up for seizures. We did not observe any side effects of Gliatilin. CONCLUSIONS: The kind of trauma and posttraumatic intracranial pathology do not determine the prognosis. The evaluation of treatment should be performed after 6-12 months. Gliatilin and Dexamin treatment improves the clinical state of patients with posttraumatic abulic state.

Synthesis and antiviral activity of some 5'-N-phthaloyl-3'-azido-2',3'-dideoxythymidine analogues.

A variety of substituted 5'-N-phthaloyl-3'-azido-2',3'-dideoxythymidine derivatives has been evaluated for their activity against HIV-1, HIV-2 and Moloney murine sarcoma virus (MSV) in cell culture. Most of the 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine) derivatives showed antiviral activity in the lower micromolar concentration range and there was a close correlation between their anti-HIV and anti-MSV activity (r = 0.99). The adamantyl phthaloyl derivative was active at submicromolar concentrations. None of the compounds showed marked cytostatic activity. They did not inhibit recombinant HIV-1 reverse transcriptase. All compounds were inactive against HIV in thymidine kinase-deficient cells, pointing to the compounds' requirement to release free AZT to afford antiviral efficacy.

Tumor necrosis factor-alpha production-regulating activity of phthalimide derivatives in genetically modified murine melanoma cells B78H1.

The effect of imides, monothioimides, trimellitimides, as well as 5'-deoxy-5'-phthaloylamino-derivatives of azidothymidine on tumor necrosis factor-alpha (TNF-alpha) production by genetically modified murine B78H1 melanoma cells transduced with the gene for human TNF-alpha (B78/TNF) was investigated. It was found that N-(adamant-1-yl)monothiophthalimide (1e) and N-(adamant-2-yl)-monothiophthalimide (1f) showed over 200% enhancing of TNF-alpha production while some of imides were inhibitors.

Health care system reform and the scope of independence in decision making by environmental/family nurses. I. Conditions for bearing responsibility for work results.

The reform of health care system, as well as the Act concerning health care units and public health insurance, provided an incentive for gaining independence by health services providers. This also pertains to environmental/family nurses who should decide on the scope of care provided and the results of nursing. Hence, a research problem was posed concerning the effect of health care system reform on the scope of independence in decision making by environmental/family nurses. This problem covered detailed questions with respect to changes in work schedule tasks, competence and responsibilities, as well as the provision of a resource base at workplaces. The study covered a total number of 110 people - 50 employed in non-public health care units and 60 in public institutions. The method of diagnostic survey and two types of statistical tests--Student's t test and 'u' test--were applied in the study. The results of the survey showed that nurses employed in new organizational forms of PHC had better conditions with respect to both their work schedules and provision of equipment at workplaces. This especially concerned a higher standard of resource base and equipment available for the staff employed on contract basis. It was confirmed that the number of nurses employed on independent contracts was small; hence a small area of independence in making decisions by environmental/family nurses.

Health care system reform and the scope of independence in decision making by environmental/family nurses. II. Evaluation of preparation of nurses for a modern model of environmental care.

Changes biased towards the autonomy of the nursing occupation originated by formal regulations do not yet designate the actual independence of nurses. This independence is determined by the modern method of work-nursing process and application in practice of a selected theory of nursing. The question pertaining to the knowledge and practical usefulness of nursing theories was justified by an anticipated positive effect of these theories on the working process. They not only indicate the goals of care, but also the scope of tasks and their type. The study was conducted by the method of a diagnostic survey with the use of questionnaire forms, and covered environmental/family nurses employed in public health care units (n=60), and non-public units (n=50). The data obtained and the results of statistical analyses allowed us to presume that environmental/family nurses do not apply the method of the nursing process, and in the majority of cases did not keep the required records. The respondents had no knowledge of international concepts of nursing. People employed in new organizational forms significantly more often referred to the theory by D. Orem, compared to those working in traditional structures.

Health care reform and the scope of independence in decision making by environmental/family nurses. III. New concept of health care and currently provided scope of services.

Until recently, corrective medicine and narrowly-understood prophylaxis have remained the focus of attention of health care staff. Various factors influenced the modification of current health activities. Providers of medical services, especially those engaged in PHC should react to the change in the concept of health care by expanding the present services offered. According to the WHO concept, dealing with healthy people is not a waste of time. Therefore, an attempt was undertaken to discover whether in the practice of environmental/family nurses, tasks were proposed to patients in the area of health promotion and prophylaxis. The studies covered 110 environmental/family nurses from the Bialystok Region. The material obtained in two groups of health care units--public and non-public--was then compared. Significant statistical differences with respect to 'very frequent' realization of health promotion programmes were observed between nurses employed in public health care units and those from non-public units. These programmes most often concerned breast feeding, and care of mother and child. In the area of prophylaxis, however, both groups undertook a 'very small' scope of actions on behalf of environment protection and prevention of three of the health problems recognized: prevention of faulty posture, dental caries and counteracting accidents, injuries and poisonings. Prophylactic tasks concerning cardiovascular system diseases, cancer, addictions and contagious diseases were more often realized.

Health care reform and the scope of independence in decision making by environmental/family nurses. IV. Contracts realized by the payer and occupational independence of nurses.

New legal and organizational conditions enabled nurses to sign contracts directly with the disposers of allocations. It was anticipated, among others, that contracting specific health services would result in the staff obtaining greater independence in the matters of nursing. Showing one's own initiative at work may lead to an increase in satisfaction among patients and nurses, as well as the strengthening of the occupational position of nurses in the future. For this reason, the study was undertaken to confirm whether PHC nurses perceive the relationship between actual independence and performing work activities within individual or group contracts. The study was conducted in a form of a diagnostic survey, and covered 120 environmental/family nurses from non-public and public health care units. The results were analyzed from the aspect of statistical differences between the experimental and control groups. A significantly greater number of staff employed on the new basis performed independent tasks in the environment, compared to nurses employed in traditional structures. Differences were also observed concerning respondents' opinions in relation to freedom in making decisions experienced in various organizational forms. According to the respondents of the experimental group, group contracts guarantee a greater autonomy, while those of the control group evaluate individual practices in more positive terms.

Synthesis and antimicrobial activity of new adamantane derivatives III.

Some novel ester imides synthesised from trimellitic acid anhydride and 1-adamantanol or 2-adamantanol, were tested as antimicrobial compounds. Unfortunately, these agents showed a modest antibacterial activity (MIC > 6 microg/ml). However, a comparison of these N-substituted adamantylester imides with the series published previously, indicated that the incorporation of L-alanine and L-phenylalanine into the phthalimide moiety was the best choice regardless of the series and leads to antimicrobial activity against Staphylococcus aureus strains.