Reactions of methylene

The research reported in this thesis concerns some reactions of the simplest organic entity - methylene.Reactivity of this species, indicative of its radical character was the reason why, though its presence in many chemical reactions was postulated in the last decade of the 19th century, the confirmation of its existence came much later, in the thirties of the present one, when the new techniques of investigation of unstable compounds such as the Paneth -mirror technique, were developed.From then till the 1950's the methylene reactions were the domain of organic chemists, who studied them mainly for their preparative applications.Invention of new analytical methods, such as mass spectrometry and gas chromatography, has enabled us to investigate these reactions quantitatively, with the prospect of elucidating the structure of methylene.The results of this work on reactions of methylene with 1,3 butadiene, butene -1, pentene -1 and tetrafluoroethylene are included in the first part of this thesis which attempts to be a survey of the methylene reactions, and can thus be regarded as the joint introduction and discussion.As the biradical nature of methylene, which would correspond to its triplet state, is still a matter of controversy and as, in many reactions methylene shows both radical and non -radical behaviour, no special division will be made between its monoradical reactions and those peculiar to biradicals, all reactions being classified into: -a) Insertionb) Abstraction and Displacement,and e) Addition reactions.The conclusions about the structure of methylene supported by studies of its reactions will be discussed in the paragraph "Structure of Methylene ".Unimolecular reactions of the cyclopropane derivatives, formed by the addition of methylene to a double bond of defins are the subject of the last paragraph in this survey

Comparative studies on cell stimulatory, permeabilizing and toxic effects induced in sensitive and multidrug resistant fungal strains by amphotericin B (AMB) and N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME)

N-Methyl-N-D-fructosyl-amphotericin B methyl ester (MFAME) is a new derivative of amphotericin B, which is characterised by low toxicity to mammalian cells and good solubility in water of its salts. The antifungal activity and effects of MFAME towards Candida albicans and Saccharomyces cerevisiae multidrug resistant MDR(+) and sensitive MDR(-) strains was compared with those of parent compound. The results obtained indicate that MDR(+) S. cerevisiae was sensitive to MFAME as well as to AMB. MFAME exhibited the same effects on fungal cells studied as parent antibiotic. The two antibiotics, depending on the dose applied induced cell stimulation, K+ efflux, and/or had a toxic effect

Gene Expression Analysis in Ovarian Cancer – Faults and Hints from DNA Microarray Study

The introduction of microarray techniques to cancer research brought great expectations for finding biomarkers that would improve patients’ treatment; however, the results of such studies are poorly reproducible and critical analyses of these methods are rare. In this study, we examined global gene expression in 97 ovarian cancer samples. Also, validation of results by quantitative RT-PCR was performed on 30 additional ovarian cancer samples. We carried out a number of systematic analyses in relation to several defined clinicopathological features. The main goal of our study was to delineate the molecular background of ovarian cancer chemoresistance and find biomarkers suitable for prediction of patients’ prognosis. We found that histological tumor type was the major source of variability in genes expression, except for serous and undifferentiated tumors that showed nearly identical profiles. Analysis of clinical endpoints [tumor response to chemotherapy, overall survival, disease-free survival (DFS)] brought results that were not confirmed by validation either on the same group or on the independent group of patients. CLASP1 was the only gene that was found to be important for DFS in the independent group, whereas in the preceding experiments it showed associations with other clinical endpoints and with BRCA1 gene mutation; thus, it may be worthy of further testing. Our results confirm that histological tumor type may be a strong confounding factor and we conclude that gene expression studies of ovarian carcinomas should be performed on histologically homogeneous groups. Among the reasons of poor reproducibility of statistical results may be the fact that despite relatively large patients’ group, in some analyses one has to compare small and unequal classes of samples. In addition, arbitrarily performed division of samples into classes compared may not always reflect their true biological diversity. And finally, we think that clinical endpoints of the tumor probably depend on subtle changes in many and, possibly, alternative molecular pathways, and such changes may be difficult to demonstrate

Polish statement on food allergy in children and adolescents

An adverse food reaction is defined as clinical symptoms occurring in children, adolescents or adults after ingestion of a food or chemical food additives. This reaction does not occur in healthy subjects. In certain individuals is a manifestation of the body hypersensitivity, i.e. qualitatively altered response to the consumed food. The disease symptoms observed after ingestion of the food can be triggered by two pathogenetic mechanisms; this allows adverse food reactions to be divided into allergic and non-allergic food hypersensitivity (food intolerance). Food allergy is defined as an abnormal immune response to ingested food (humoral, cellular or mixed). Non-immunological mechanisms (metabolic, pharmacological, microbiological or other) are responsible for clinical symptoms after food ingestion which occur in non-allergic hypersensitivity (food intolerance). Food allergy is considered a serious health problem in modern society. The prevalence of this disorder is varied and depends, among other factors, on the study population, its age, dietary habits, ethnic differences, and the degree of economic development of a given country. It is estimated that food allergy occurs most often among the youngest children (about 6-8% in infancy); the prevalence is lower among adolescents (approximately 3-4%) and adults (about 1-3%). The most common, age-dependent cause of hypersensitivity, expressed as sensitization or allergic disease (food allergy), are food allergens (trophoallergens). These are glycoproteins of animal or plant origine contained in: cow's milk, chicken egg, soybean, cereals, meat and fish, nuts, fruits, vegetables, molluscs, shellfish and other food products. Some of these allergens can cause cross-reactions, occurring as a result of concurrent hypersensitivity to food, inhaled or contact allergens. The development of an allergic process is a consequence of adverse health effects on the human body of different factors: genetic, environmental and supportive. In people predisposed (genetically) to atopy or allergy, the development of food allergy is determined by four allergic-immunological mechanisms, which were classified and described by Gell-Coombs. It is estimated that in approximately 48-50% of patients, allergic symptoms are caused only by type I reaction, the IgEmediated (immediate) mechanism. In the remaining patients, symptoms of food hypersensitivity are the result of other pathogenetic mechanisms, non-IgE mediated (delayed, late) or mixed (IgE mediated, non-IgE mediated). Clinical symptomatology of food allergy varies individually and depends on the type of food induced pathogenetic mechanism responsible for their occurrence. They relate to the organ or system in which the allergic reaction has occurred (the effector organ). Most commonly the symptoms involve many systems (gastrointestinal tract, skin, respiratory system, other organs), and approximately 10% of patients have isolated symptoms. The time of symptoms onset after eating the causative food is varied and determined by the pathogenetic mechanism of the allergic immune reaction (immediate, delayed or late symptoms). In the youngest patients, the main cause of food reactions is allergy to cow’s milk. In developmental age, the clinical picture of food allergy can change, as reflected in the so-called allergic march, which is the result of anatomical and functional maturation of the effector organs, affected by various harmful allergens (ingested, inhaled, contact allergens and allergic cross-reactions). The diagnosis of food allergy is a complex, long-term and time-consuming process, involving analysis of the allergic history (personal and in the family), a thorough evaluation of clinical signs, as well as correctly planned allergic and immune tests. The underlying cause of diagnostic difficulties in food allergy is the lack of a single universal laboratory test to identify both IgE-mediated and non-IgE mediated as well as mixed pathogenetic mechanisms of allergic reactions triggered by harmful food allergens. In food allergy diagnostics is only possible to identify an IgE-mediated allergic process (skin prick tests with food allergens, levels of specific IgE antibodies to food allergens). This allows one to confirm the diagnosis in patients whose symptoms are triggered in this pathogenetic mechanism (about 50% of patients). The method allowing one to conclude on the presence or absence of food hypersensitivity and its cause is a food challenge test (open, blinded, placebo-controlled). The occurrence of clinical symptoms after the administration of food allergen confirms the cause of food allergy (positive test) whereas the time elapsing between the triggering dose ingestion and the occurrence of clinical symptoms indicate the pathogenetic mechanisms of food allergy (immediate, delayed, late). The mainstay of causal treatment is temporary removal of harmful food from the patient’s diet, with the introduction of substitute ingredients with the nutritional value equivalent to the eliminated food. The duration of dietary treatment should be determined individually, and the measures of the effectiveness of the therapeutic elimination diet should include the absence or relief of allergic symptoms as well as normal physical and psychomotor development of the treated child. A variant alternative for dietary treatment of food allergy is specific induction of food tolerance by intended contact of the patient with the native or thermally processed harmful allergen (oral immunotherapy). This method has been used in the treatment of IgE-mediated allergy (to cow's milk protein, egg protein, peanut allergens). The obtained effect of tolerance is usually temporary. In order to avoid unnecessary prolongation of treatment in a child treated with an elimination diet, it is recommended to perform a food challenge test at least once a year. This test allows one to assess the body's current ability to acquire immune or clinical tolerance. A negative result of the test makes it possible to return to a normal diet, whereas a positive test is an indication for continued dietary treatment (persistent food allergy). Approximately 80% of children diagnosed with food allergy in infancy "grow out" of the disease before the age of 4-5 years. In children with non-IgE mediated food allergy the acquisition of food tolerance is faster and occurs in a higher percentage of treated patients compared to children with IgE-mediated food allergy. Pharmacological treatment is a necessary adjunct to dietary treatment in food allergy. It is used to control the rapidly increasing allergic symptoms (temporarily) or to achieve remission and to prevent relapses (long-term treatment). Preventive measures (primary prevention of allergies) are recommended for children born in a "high risk" group for the disease. These are comprehensive measures aimed at preventing sensitization of the body (an appropriate way of feeding the child, avoiding exposure to some allergens and adverse environmental factors). First of all, the infants should be breast-fed during the first 4-6 months of life, and solid foods (non milk products, including those containing gluten) should be introduced no earlier than 4 months of age, but no later than 6 months of age. An elimination diet is not recommended for pregnant women (prevention of intrauterine sensitization of the fetus and unborn child). The merits of introducing an elimination diet in mothers of exclusively breast-fed infants, when the child responds with allergic symptoms to the specific diet of the mother, are disputable. Secondary prevention focuses on preventing the recurrence of already diagnosed allergic disease; tertiary prevention is the fight against organ disability resulting from the chronicity and recurrences of an allergic disease process. Food allergy can adversely affect the physical development and the psycho-emotional condition of a sick child, and significantly interfere with his social contacts with peers. A long-term disease process, recurrence of clinical symptoms, and difficult course of elimination diet therapy are factors that impair the quality of life of a sick child and his family. The economic costs generated by food allergies affect both the patient's family budget (in the household), and the overall financial resources allocated to health care (at the state level). The adverse socio-economic effects of food allergy can be reduced by educational activities in the patient’s environment and dissemination of knowledge about the disease in the society

Aromaticity Effect on Supramolecular Aggregation. Aromatic vs. Cyclic Monohydroxy Alcohols

In this paper, the steric hindrance effect related to the presence of either an aromatic or cyclic ring on the self-association process in the series of monohydroxy alcohols (MAs), from cyclohexanemethanol to 4-cyclohexyl-1-butanol and from benzyl alcohol to 4-phenyl-1- butanol, was studied using X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Broadband Dielectric Spectroscopy (BDS) and the Pendant Drop (PD) methods. Based on FTIR results, it was shown that phenyl alcohol (PhA) and cyclohexyl alcohol (CA) derivatives reveal substantial differences in the association degree, the activation energy of dissociation, and the homogeneous distribution of supramolecular nanoassociates suggesting that the phenyl ring exerts a stronger steric impact on the self-assembling of molecules than cyclohexyl one. Additionally, XRD data revealed that phenyl moiety introduces more heterogeneity in the organization of molecules compared to the cyclic one. The changes in the self-association process of alcohols were also reflected in differences in the molecular dynamics of the H-bonded aggregates, as well as in the Kirkwood factor, defining the long-range correlation between dipoles, which were slightly higher for CAs with respect to those determined for PhAs. Unexpectedly it was also found that the surface layers of PhAs were more organized than those formed by CAs. Thus, these findings provided insight into the impact of aromaticity on the self–assembly process, Hbonding pattern, supramolecular structure, and intermolecular dynamics of the studied alcohols

The role of neuronal apoptosis inhibitory protein (NAIP) in acute myeloid leukemia patients

Acute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L ( = 0.009, = 0.033, and = 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo ( = 0.025 and = 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy ( = 0.033, < 0.001, and < 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo, AML, and a low NAIP expression ( = 0.03, = 0.024, and = 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo ( = 0.009) and AML ( = 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy

Myśl i polityka: księga pamiątkowa dedykowana profesorowi Jackowi Marii Majchrowskiemu T. 2

Publikacja jubileuszowa z okazji 40-lecia pracy naukowej profesora Jacka Majchrowskieg

Arbuscular mycorrhiza of herbs colonizing a salt affected area near Kraków (Poland)

The arbuscular mycorrhizal (AM) status of plants colonizing an area affected by leakage of salty water (Barycz near Kraków, Poland) was studied in 2000 and 2001. The occurrence of plants typical for soils of increased salinity was observed. Among the 13 examined plant species 7 were mycorrhizal. The abundance of mycorrhizal plant populations was increased in the second year of study. Strains of 4 species of AMF, including Glomus caledonium, G. claroideum, G. geosporum and G. intraradices were isolated using trap cultures. On the basis of morphological characters the presence of G. tenue was detected in plant roots of several species from the study area. The efficiency of mycorrhizal colonization and arbuscule formation by two strains of G. geosporum isolated from a saline area and a strain of G. intraradices from unaffected sites was tested in an experiment carried out on Plantago lanceolata cultivated on substrata of different salinity levels. The increase in mycorrhizal parameters with growing salt content was observed in the case of strains originating from the salt-affected area. At the highest salt level these strains formed better developed mycorrhiza than the strain from the non-saline site, suggesting a better adaptation of the strains from the saline area. The data on vitality (alkaline phosphatase test) of intraradical AM fungi gave a clearer picture than those obtained by the conventional aniline blue staining

Arbuscular mycorrhiza of herbs colonizing a salt affected area near Kraków (Poland)

The arbuscular mycorrhizal (AM) status of plants colonizing an area affected by leakage of salty water (Barycz near Kraków, Poland) was studied in 2000 and 2001. The occurrence of plants typical for soils of increased salinity was observed. Among the 13 examined plant species 7 were mycorrhizal. The abundance of mycorrhizal plant populations was increased in the second year of study. Strains of 4 species of AMF, including Glomus caledonium, G. claroideum, G. geosporum and G. intraradices were isolated using trap cultures. On the basis of morphological characters the presence of G. tenue was detected in plant roots of several species from the study area. The efficiency of mycorrhizal colonization and arbuscule formation by two strains of G. geosporum isolated from a saline area and a strain of G. intraradices from unaffected sites was tested in an experiment carried out on Plantago lanceolata cultivated on substrata of different salinity levels. The increase in mycorrhizal parameters with growing salt content was observed in the case of strains originating from the salt-affected area. At the highest salt level these strains formed better developed mycorrhiza than the strain from the non-saline site, suggesting a better adaptation of the strains from the saline area. The data on vitality (alkaline phosphatase test) of intraradical AM fungi gave a clearer picture than those obtained by the conventional aniline blue staining