One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates.

A one-pot lithiation-phosphonylation procedure was elaborated as a method to prepare heteroaromatic phosphonic acids. It relied on the direct lithiation of heteroaromatics followed by phosphonylation with diethyl chlorophosphite and then oxidation with hydrogen peroxide. This protocol provided the desired phosphonates with satisfactory yields. This procedure also had some limitations in its dependence on the accessibility and stability of the lithiated heterocyclic compounds. The same procedure could be applied to phosphonylation of aromatic compounds, which do not undergo direct lithiation and thus require the use of their bromides as substrates. The obtained compounds showed weak antiproliferative activity when tested on three cancer cell lines.

Determination of bisphosphonates anti-resorptive properties based on three forms of ceramic materials: Sorption and release process evaluation.

There is a strong need to search for more effective compounds with bone anti-resorptive properties, which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite (HA), this study used three forms of ceramic materials, two of which are bone-stimulating materials, to assess the suitability of new active substances with anti-resorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA (a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction (MINE) device (a polymer inert skeleton), respectively, were used. The affinity of risedronate (a standard compound) and sixteen aminomethylenebisphosphonates (new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorption-desorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.

Determination of bisphosphonates anti-resorptive properties based on three forms of ceramic materials:Sorption and release process evaluation / 药物分析学报

There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates.To achieve this goal,it is necessary to search for new techniques to characterize the interactions between bone and drug.By studying their interaction with hydroxyapatite (HA),this study used three forms of ceramic materials,two of which are bone-stimulating materials,to assess the suitability of new active substances with anti-resorptive properties.In this study,three methods based on HA in loose form,polycaprolactone/HA (a polymer-ceramic materials containing HA),and polymer-ceramic monolithic in-needle extraction(MINE) device (a polymer inert skeleton),respectively,were used.The affinity of risedronate (a standard compound) and sixteen aminomethylenebisphosphonates (new compounds with potential anti-resorptive properties) to HA was defined according to the above-mentioned methods.Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied,of which one was selected for more-detailed further research.Simulated body fluids containing bisphosphonates were passed through the MINE device.In this way,sorption-desorption of bisphosphonates was evaluated using this MINE device.The paper presents the advantages and disad-vantages of each technique and its suitability for assessing new active substances.All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate,in hope that it reflects their higher bone affinity and release ability.

Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products.

A three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties-the corresponding tetraphosphonic acids-were obtained. In the cases of 1,2-diaminobenzene, 1,2-diaminocyclohexanes and 1,2-diaminocyclohexenes, only one amino group reacted. This is most likely the result of the formation of hydrogen bonding between the phosphonate oxygen and a hydrogen of the adjacent amino group, which caused a decrease in the reactivity of the amino group. Most of the obtained compounds inhibited the proliferation of RAW 264.7 macrophages, PC-3 human prostate cancer cells, and MCF-7 human breast cancer cells, with 1, trans-7, and 16 showing broad nonspecific activity, which makes these compounds especially interesting in the context of anti-osteolytic treatment and the blocking of interactions and mutual activation of osteoclasts and tumor metastatic cells. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid, which were used as controls. However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption.

Thermodynamics of the Interactions of Aminobisphosphonates and Their Calcium Complexes with Bovine Serum Albumin.

Binding of bisphosphonates (BPs) to plasma proteins was investigated in the 1990s as a pharmacokinetic issue in order to fully understand bio-distribution of BP drugs which are successfully used for the treatment of several bone-related diseases. It has been hypothesized that binding to these proteins occurs with low to moderate affinity despite of unfavorable hydrophilicity of BPs, and Ca2+ was identified as a strong catalyst of this binding. However, these studies mainly consisted in the separation and quantification of bound and unbound drug or protein fractions using chromatographic techniques without an outcome on the molecular level. Presented thermodynamic studies analyze the interactions of three N-BPs as well as their Ca2+ complexes with bovine serum albumine (BSA) by means of isothermal calorimetry. The studies reveal spontaneous enthalpy favored interactions of N-BPs (amino-containing BPs) with BSA, which are enhanced by the presence of Ca2+ ions up to ~15-fold, strongly depending on N-BP. Those are low affinity binding events, comparable to Ca2+ -N-BP interactions, which most likely occur at Ca2+ binding site(s). It is a first example of estimation of thermodynamic forces of interactions of free and calcium-bound N-BPs with albumin.

The Influence of Cigarette Smoke Exposure on the Copper Concentration in the Serum Depending on the Use of Menopausal Hormone Therapy.

This study evaluated the effect of menopausal hormone therapy (MHT) on serum concentration of copper in postmenopausal women depending on passive or active exposure to tobacco smoke or lack thereof. The study included healthy postmenopausal women aged 42-69 years, who used (n = 76) or did not use (n = 76) MHT. Salivary cotinine and serum copper concentrations were determined in all the study subjects. Salivary cotinine exceeded 14 ng/ml in 14 women from the MHT group (18.5%) and in 16 controls (21.1%). Up to 41 (27%) study subjects had serum copper above the upper normal limit (1.17 mg/l). No correlation was found between salivary cotinine and serum copper in women with cotinine concentrations <14 ng/ml, and these two parameters correlated weakly in subjects with cotinine >14 ng/ml. Salivary concentration of cotinine increased with serum copper level in the MHT group, but not in the controls; smokers using MHT presented with significantly higher serum copper than nonsmokers. These findings imply that MHT does not affect serum concentration of copper in women who are not exposed to tobacco smoke. However, MHT seems to contribute to unfavorable increase in serum copper in passive and active smokers.

Three-Component Reaction of Benzylamines, Diethyl Phosphite and Triethyl Orthoformate: Dependence of the Reaction Course on the Structural Features of the Substrates and Reaction Conditions.

The reaction between benzyl amines, triethyl orthoformate, and diethyl phosphite affords either bisphosphonic (compound 1) or N-benzylaminobenzylphosphonic (compound 2) acid depending on the reaction conditions. The final output of the reaction can be manipulated by the choice of reaction conditions, particularly the molar ratio of substrates.

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products.

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

Synthetic Procedures Leading towards Aminobisphosphonates.

Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

[Functional limitations associated with lumbosacral spine pain in pregnant women].

Introduction: Lower back pain affects most pregnant women. Pain is often associated with varying degrees of functional limitations, causing a problem for pregnant women in the performance of many everyday activities. The aim of the study was to assess the extent to which lumbosacral spine pain caused limitations in the daily functioning of pregnant women, and the relationship between reported restrictions and analysed variables. Material and methods: The study was conducted in the city of Szczecin in Poland among 81 pregnant women. Data were collected using a standardized Oswestry questionnaire survey (The Oswestry Lower Back Pain Disability Questionnaire). Results were analysed using the χ² test of independence. The signiô€icance level was adopted at p < 0.05. Results: The majority of women pregnant for the second time (n = 38) had mild disability. The relationship between the degree of disability and the order of pregnancies was statistically signi ô€icant (χ² = 40.457, p = 0.0000000085). Conclusions: The majority of pregnant women had minor functional limitations due to pain in the lumbosacral spine region. The degree of functional limitations depends on the trimester of pregnancy and the order of pregnancies.

[Kinesiotaping as an interdisciplinary therapeutic method].

Introduction: Kinesiotaping (KT) is one of the newest methods commonly used in many medical sciences: neurology, orthopaedics and traumatology, oncology, gynaecology and obstetrics, and in paediatrics. Due to its special properties, KT can be used depending on individual needs and problems during rehabilitation. Aim: This article presents a systematic review of the clinical effectiveness of using KT in physiotherapy. Conclusions: KT method is widespread in different medical sciences and is a good method supporting rehabilitation and pharmacological treatment. Due to its special properties it can be used in children, adults, and also pregnant women.

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues.

A convenient approach has been developed to α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues by α-phosphonylation, α-phosphinylation or α-phosphinoylation of 1-(N-acylamino)alkylphosphonates, that, in turn, are easily accessible from N-acyl-α-amino acids. Effective electrophilic activation of the α-position of 1-(N-acetylamino)alkylphosphonates was achieved by electrochemical α-methoxylation of these compounds in methanol, mediated with NaCl, followed by displacement of the methoxy group with triphenylphosphonium tetrafluoroborate to give hitherto unknown 1-(N-acetylamino)-1-triphenylphosphoniumalkylphosphonate tetrafluoroborates. The latter compounds react smoothly with trialkyl phosphites, dialkyl phosphonites or alkyl phosphinites in the presence of Hünig's base and methyltriphenylphosphonium iodide in a Michaelis-Arbuzov-like reaction to give the expected alkylidenebisphosphonates, 1-phosphinylalkylphosphonates or 1-phosphinoylalkylphosphonates, respectively, in good yields.

[Physical activity as a factor reducing aggressive behaviour in adolescents in gymnasium school age].

Introduction: Violence among adolescents is one of the most serious problems, and has significantly increased in recent years. Studies conducted in 2011 on aggression and violence in schools reported that the most widespread form of offence is verbal aggression. As many as 63% of students had experience of being ridiculed, humiliated or offended. According to research, 33% of students suffered from physical aggression (PA). The aim of the study to evaluate the relationship between physical activity and the incidence of aggressive behaviour in adolescents of lower -secondary school age. Material and methods: The study was conducted in autumn 2013, in West Pomerania province in Poland, among 807 students of a lower -secondary school. A diagnostic survey method with a standardized questionnaire (Aggression Questionnaire) by H. Buss and M. Perry of 1992 (Amity version) was used. Statistical analysis was performed in Statistica Pl version 10 using the Kruskal­Wallis test and the U Mann­Whitney test with a significance level of p ≤ 0.05. Results: The Kruskal­Wallis test showed only a statistically significant difference between the groups surveyed in relation to the frequency of attendance at additional sports activities and the level of PA (p = 0.02). Conclusions: Subjects who engage in team sports show a higher tendency for physical aggression than those engaged in individual sports. Taking into account the higher level of PA in adolescents performing sport 3­4 times a week compared to physically inactive and very active adolescents (more than 5 times a week), it may be presumed that sport attracts people with high physical aggression tendencies. Only with strong involvement in sport is the level of aggression reduced. There is a need for research on the personality of young athletes, which would give credence to this thesis.

[A comparison of opinions about disabled sports between students of University in Szczecin and disabled athletes ]. / Porównanie opinii wsród niepelnosprawnych sportowców i studentów uniwersytetu szczecinskiego na temat sportu inwalidzkiego.

INTRODUCTION: Sport among disabled people is becoming more and more popular. It is happening mostly due to the growing number of sports centres for the disabled, and the widespread popularization of this form of activity by organi- zations working for the benefit of disabled people. Also, the mass media play an important role in the process. The aim of the study a comparison of the knowledge and opinions about disabled sports of physical education students and disabled athletes. METHODS: The research was conducted using two dif- ferent questionnaires. One of them was given to students of Physical Education, the other to members of a disabled sports club, "Start". The questionnaires consisted of two sections: a personal profile, and 17 questions about disabled sports. 45 full-time students of Physical Education at the University of Szczecin: 30 (66.7%) women and 15 (33.3%) men. The average age of the group was 23.6 years. The second group, from the disabled sports club, consisted of 33 people, 18 (54.5%) women and 15 (45.5%) men; the aver- age age of the participants was 28.6 years. RESULTS: Among the disabled people, 10 (30.3%) people were unable to name any disabled athlete; among the. group of able-bodied students, there were 33 (73.3%) people who were not able to do the same thing. According to students, disabled people do sports mainly for rehabilitation purposes (51.1%). According to the disabled students' group, however, sport for disabled people means satisfaction and higher self-esteem (36.36%). When it comes to the best source of information on the subject, television proved to be the best one among the media. The able-bodied students rated their knowledge of disabled sports as satisfactory (66.7%), while only 6% of disabled students considered the knowledge of able-bodied people about disabled sports to be satisfactory. CONCLUSIONS: 1. The knowledge about disabled sports among students of physical education is superficial. The disabled also do not possess an extensive knowledge about disabled sports. 2. Opinion on the importance of sport in the lives of disabled people differ between the research groups. Able-bodied people see the role of sport mainly as a rehabilitation tool; disabled people, however, see it as an activity giving satisfaction and raising their self-esteem.

Assesment of psychosocial work conditions of nurses at selected hospital wards.

BACKGROUND: Good organisation of work, clear division of responsibilities, support from superiors are factors that positively influence the satisfaction of the profession. The purpose of the work was the assessment of psychosocial working conditions of nurses. MATERIAL AND METHODS: The research included 388 nurses working at surgical wards, medical treatment wards, and psychiatric wards. The research method was a diagnostic survey carried out by means of a questionnaire called Psychosocial Work Conditions. The obtained results were statistically analysed. RESULTS: Nearly a half of the nurses considers the requirements at work as moderate, and 36.66% as high. Nurses from medical treatment wards indicate the highest level of requirements. Nurses working at psychiatric wards and in a shift system significantly more often feel the requirements relating to overload and resulting from a conflict of roles. Nurses working in the profession for more than 10 years considerably more often describe the level of behavioural control as high in comparison to those working for a shorter time. Regardless of the character of a ward, nurses most often (44.33%) assess the support from co-workers as average, and 1/5 considered this as low. CONCLUSIONS: The results indicate the correctness of introducing psychosocial training for professionally active nurses.

Health behaviors of postmenopausal women.

INTRODUCTION: Health status and health-related quality of life of postmenopausal women are issues, which nowadays pose a serious challenge to many domains of science. Climacteric symptoms which occur at this stage of life, lower its quality and make a negative contribution to self-reported health status, are mostly observed in a particular group of women. Evaluation of health behaviors performed using a standardized questionnaire, the Health Behavior Inventory (HBI), may help establish a comprehensive diagnosis of women's health, and thus select effective interventions. A systemic approach to menopause assumes that full fitness of women and good quality of their lives can be maintained not only by means of pharmacotherapy but also other forms of action, especially health education oriented towards changes in the lifestyle and promotion of healthy behaviors. THE AIM OF THIS STUDY: Aim of the study is to perform a HBI-based assessment of women's health behaviors in such categories as healthy eating habits (HEH), preventive behaviors (PB), positive mental attitudes (PMA), and health practices (HP). MATERIAL AND METHODS: The study involved 151 healthy postmenopausal women. A research tool was a standardized questionnaire, the Health Behavior Inventory (HBI). RESULTS: The surveyed women obtained 70% of the maximum score on average, which suggests a medium level of health behaviors in this group. The levels of health behaviors in the categories of positive mental attitudes and health practices significantly differed between older women and their younger counterparts (higher levels were observed among older respondents). There were also significant differences in the levels of healthy behaviors between women with secondary and higher education (those better educated declared healthy behaviors more often). There was no correlation between the level of health behaviors and the BMI of the surveyed women. CONCLUSIONS: Older women attached greater importance to positive mental attitudes, and so they avoided tension, stress and depressing situations. They also attached more weight to health practices (HP), i.e. the number of hours devoted to sleeping, resting and physical activity. The main determinant of a healthy lifestyle was higher education.

[POLISH CITIZENS' OPINIONS CONCERNING CO-PAYMENT FOR HOSPITALIZATION AND SUBSIDIES FOR NON-STANDARD BENEFITS]. / OPINIE POLAKÓW O WSPÓLPLACENIU ZA LECZENIE SZPITALNE ORAZ O DOPLATACH DO SWIADCZEN PONADSTANDARDOWYCH.

INTRODUCTION: Co-payment in the health sector operates in most healthcare systems in European countries. The aim of this study was knowledge of Polish citizens' opinions concerning healthcare services co-payment with respect to selected socio-demographic factors. MATERIAL AND METHODS: The study was conducted using a diagnostic survey of 636 respondents, representing residents of the West Pomeranian region, Poland. RESULTS: The majority of respondents did not accept co-payment for health services. CONCLUSIONS: Material situation and educational background impact on decisions concerning co-payment for hospital treatment.

The analysis of a personality profile of selected groups of nurses.

AIM: The analysis of a personality profile of selected groups of Polish nurses. MATERIAL AND METHODS: 72 nurses working in internal diseases departments and departments of surgery in Szczecin were investigated. To examine the personality profiles a diagnostic survey was used. It was based on an authorised Polish elaboration of Cattell's 16 Personality Factors Test. To examine their personality profile an authorised Polish elaboration of a diagnostic survey based on a standardized elaboration of personality profiles by Raymond B. Cattell was used. RESULTS: The analysis of the results indicated no significant differences between groups. The average sten scores from each of 16 examined factors were within the established limits. CONCLUSIONS: The personality profiles of the examined groups of nurses indicated a greater probability of the appearance of desirable features among the investigated people working in medical professions and demanding team cooperation, as well as relationship-building skills. Nurses, regardless of workplace, had personality traits indicating the need for education and improving occupational qualifications.

[Evaluation of the quality of medical services by patients including selected sociodemographic variables]. / Ocena jakosci uslug medycznych przez pacjentów z uwzglednieniem wybranych zmiennych socjodemograficznych.

INTRODUCTION: Medical health care centres should aim at the application of a two-dimensional concept of quality--technical quality and functional quality. Technical quality means the compliance with norms and technical requirements which apply to medical services that are provided to patients. This concerns medical standards, technology and the competence of medical staff. Functional quality, which means the subjective estimate of patients, is an additional benefit for the patient and it becomes the best competitive advantage in conditions of comparable technical levels of provided medical services. The patient will be satisfied with medical services if these elements are balanced. The aim of the study was the evaluation of the quality of functional services in a specialist outpatient clinic in the Szczecin area by patients. MATERIAL AND METHODS: 200 randomly-chosen patients of specialist outpatient clinics in Szczecin were asked to estimate the functional quality of services in specialist outpatient clinics. A questionnaire was used. The results were subjected to statistical analysis. RESULTS: Most of the patients--51.3% had confidence in their physician. 52.34% of the patients claimed that their doctor was not interested in their problems. Almost half of the respondents--47.92% stated that there was no telephone contact with their doctor. CONCLUSIONS: It is necessary to educate future physicians in problems of interpersonal communication.

[Health care units image development on the market of medical services]. / Ksztaltowanie wizerunku placówek ochrony zdrowia na rynku uslug medycznych.

The cause for this document is to present a deliberation on public health facility image development on the medical services market. Marketization of the health service, growing awareness of Polish citizens and their expectation of high service quality as well as increased competition in the healthcare system market is the reason why health unit managers need to put a lot of strength and effort in sustaining or improving the image of the facility they run. Such action gives a chance for obtaining a competitive advantage.