Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis.

Arginine, due to the guanidine moiety, increases peptides' hydrophilicity and enables interactions with charged molecules, but at the same time, its presence in a peptide chain might reduce its permeability through biological membranes. This might be resolved by temporary coverage of the peptide charge by lipophilic, enzyme-sensitive alkoxycarbonyl groups. Unfortunately, such a modification of a guanidine moiety has not been reported to date and turned out to be challenging. Here, we present a new, optimized strategy to obtain arginine building blocks with increased lipophilicity that were successfully utilized in the solid-phase peptide synthesis of novel arginine vasopressin prodrugs.

Emotional Decoding Abilities Do Not Influence Neuropsychiatric Disturbances in Patients With Frontotemporal Dementia.

The ability to accurately recognize emotional information belongs to very important interpersonal communication skills in humans. Disturbance of emotional processing is present in behavioral variant of frontotemporal dementia (bvFTD), and the severity of pathological behavior may be linked to misunderstanding of other people's emotions. In our study, we examined hypothesis that patients with worse ability to decode emotions have more behavioral and psychopathological disturbances--the most challenging manifestations of dementia--than those who decode emotions better. We were not able to prove this hypothesis. The ability to decode emotions in patients with bvFTD did not influenced their behavior.

[Influence of spectral interferences on the results of quartz determination by infrared spectrometry]. / Wplyw interferencji spektralnych na wyniki oznaczen kwarcu metoda spektrometrii w podczerwieni.

BACKGROUND: Determination of quartz by Fourier transform infrared spectrometry (FTIR) is not specific: the obtained results are influenced by matrix components, some of which cause spectral interference. The aim of the study was to evaluate the effect of dust components responsible for spectral interference with quartz on the results of its determinations, and to develop methods to minimize the effects of interferences. MATERIAL AND METHODS: Investigation of interferent effects were conducted using respirable dusts: quartz SRM 1878a, cristobalite SRM 1879a, synthetic amorphous silica (Zeosil) and feldspar, albite and kaolinite. For the study 17 mixtures with quartz and interferents at concentrations from 10 to 90% were prepared. Determinations of quartz were carried out by the KBr disc method. RESULTS: In mixtures of quartz with interferents, the results based on bands 798-779 cm-1 were overestimated by 10-55%, while those based on band 695 cm-1 were closer to the true content of quartz. It was found that the best methods able to decrease the impact of spectral interference are: scaled subtraction of IR spectra of feldspar or kaolinite analysed in nonashed samples, correction curve for kaolinite also investigated in nonashed samples with quartz-content calculation based on band 695 cm-1 in mixtures with cristobalite, amorphous silica or kaolinite in ashed samples. CONCLUSIONS: The study indicates the need to identify spectral interferences in dust when determining crystalline silica by FT-IR and to take actions to minimize their impact on the obtained results.

Health effects of occupational exposure to crystalline silica in the light of current research results.

Crystalline silica is commonly found in the work environment. Possible health effects of occupational exposure continue to be the subject of extensive research. The aim of this paper was to analyze the recent findings concerning the health effects of exposure to crystalline silica, taking into account different levels of exposure. This work is based on the relevant information from the papers retrieved from the following databases: EBSCO, Scopus, ScienceDirect, and Web of Science, using the following keywords: crystalline silica, quartz, health effects. The review of the results confirms the multi-faceted harmful effects of crystalline silica. Prolonged occupational exposure, apart from silicosis and non-cancer respiratory diseases, may also result in the development of lung cancer, and autoimmune and chronic kidney diseases, the pathogenesis, which has not been completely explained yet. The exposure to the crystalline silica at concentrations close to the current occupational exposure limit value does not exclude the risk of the following pathologies: silicosis, lung cancer, other lung diseases and renal diseases. It is not feasible to completely eliminate the crystalline silica dust from the work environment. The best way to reduce the health effects of the exposure is to minimize the concentrations of silica dust. Further progress in clarifying the true mechanisms of interaction between silica dust and lung cells, the determination of the importance of surface properties of the silica particles in the pathogenic processes and explaining the effects of co-morbid dust in the work environment may help to prevent the harmful effects of silica dust.

Cyclic Peptidic Furin Inhibitors Developed by Combinatorial Chemistry.

Furin is a human serine protease responsible for activating numerous physiologically relevant cell substrates and is also involved in the development of various pathological conditions, including inflammatory diseases, cancers, and viral and bacterial infections. Therefore, compounds with the ability to inhibit furin's proteolytic action are regarded as potential therapeutics. Here we took the combinatorial chemistry approach (library consisting of 2000 peptides) to obtain new, strong, and stable peptide furin inhibitors. The extensively studied trypsin inhibitor SFTI-1 was used as a leading structure. A selected monocylic inhibitor was further modified to finally yield five mono- or bicyclic furin inhibitors with values of K i in the subnanomolar range. Inhibitor 5 was the most active (K i = 0.21 nM) and significantly more proteolytically resistant than the reference furin inhibitor described in the literature. Moreover, it reduced furin-like activity in PANC-1 cell lysate. Detailed analysis of furin-inhibitor complexes using molecular dynamics simulations is also reported.

[Application of infrared spectrometry (FT-IR) for mineral identification of asbestos in bulk samples]. / Zastosowanie spektrometrii w podczerwieni (FT-IR) do identyfikacji azbestu w próbkach materialowych.

BACKGROUND: The aim of this study was to apply infrared spectrometry (FTIR) in mineral identification of asbestos in bulk materials. MATERIAL AND METHODS: The identification of asbestos was based on infrared spectra of UICC and NIST: SRM 1866a and SRM 1867 standard asbestos, and infrared spectra of heat treatment chrysotile, crocidolite and amosite asbestos. The samples of bulk materials were grinded and fibers were isolated from samples. The KBr disc standard technique was used in the preparation of samples for infrared measurements. The infrared spectra were recorded in transmittance function, at resolution of 4 cm1 and for 32 averaged scans. RESULTS: The analysis of the infrared spectra revealed that chrysotile, crocidolite, amosite and anthophyllite asbestos can be identified in industrial products and distinguished in mixtures. Spectra of fibrous materials do not interfere with spectra of asbestos. When analyzing the whole sample mass, interferences from the components of construction materials can be eliminated or reduced by using computer transforming spectra, preliminary purification of samples or separation of sample components. The method used permit to identify from 2 to 4 microg of the three basic forms of asbestos. Spectra of chrysotile and amosite heated to 500 degrees C and crocidolite heated to 300 degrees C are the same as non-heated forms. Heating in higher temperature induces characteristic changes in spectra and the transformation of asbestos into other minerals. CONCLUSIONS: Infrared spectrometry can be used for routine identification of asbestos in samples of bulk materials also treated with high temperature, and to assess the effectiveness of asbestos waste detoxification.

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications.

Bowman-Birk inhibitors (BBIs) are found primarily in seeds of legumes and in cereal grains. These canonical inhibitors share a highly conserved nine-amino acids binding loop motif CTP1SXPPXC (where P1 is the inhibitory active site, while X stands for various amino acids). They are natural controllers of plants' endogenous proteases, but they are also inhibitors of exogenous proteases present in microbials and insects. They are considered as plants' protective agents, as their elevated levels are observed during injury, presence of pathogens, or abiotic stress, i.a. Similar properties are observed for peptides isolated from amphibians' skin containing 11-amino acids disulfide-bridged loop CWTP1SXPPXPC. They are classified as Bowman-Birk like trypsin inhibitors (BBLTIs). These inhibitors are resistant to proteolysis and not toxic, and they are reported to be beneficial in the treatment of various pathological states. In this review, we summarize up-to-date research results regarding BBIs' and BBLTIs' inhibitory activity, immunomodulatory and anti-inflammatory activity, antimicrobial and insecticidal strength, as well as chemopreventive properties.

Occupational exposure assessment for crystalline silica dust: approach in Poland and worldwide.

Crystalline silica is a health hazard commonly encountered in work environment. Occupational exposure to crystalline silica dust concerns workers employed in such industries as mineral, fuel-energy, metal, chemical and construction industry. It is estimated that over 2 million workers in the European Union are exposed to crystalline silica. In Poland, over 50 thousand people work under conditions of silica dust exposure exceeding the occupational exposure limit. The assessment of occupational exposure to crystalline silica is a multi-phase process, primarily dependent on workplace measurements, quantitative analyses of samples, and comparison of results with respective standards. The present article summarizes the approaches to and methods used for assessment of exposure to crystalline silica as adopted in different countries in the EU and worldwide. It also compares the occupational limit values in force in almost 40 countries. Further, it points out the consequences resulting from the fact that IARC has regarded the two most common forms of crystalline silica: quartz and cristobalite as human carcinogens. The article includes an inter-country review of the methods used for air sample collection, dust concentration measurements, and determination of crystalline silica. The selection was based on the GESTIS database which lists the methods approved by the European Union for the measurements and tests regarding hazardous agents. Special attention has been paid to the methods of determining crystalline silica. The author attempts to analyze the influence of analytical techniques, sample preparation and the reference materials on determination results. Also the operating parameters of the method, including limit of detection, limit of quantification, and precision, have been compared.

[Backgrounds for assessing occupational exposure to crystalline silica dust in Poland and worldwide]. / Podstawy oceny narazenia zawodowego na pyl krystalicznej krzemionki w Polsce i na swiecie.

Crystalline silica is an agent harmful to human health, and quite frequently present in occupational environments. Occupational groups exposed to crystalline silica dust include mostly workers of the mineral and coal mining as well as metallurgical, chemical and construction industries. In the European Union (EU), the number of those exposed to this agent is estimated at over 2 million persons. In Poland, the number of people employed under conditions of excessive silica dust exposure exceeds 50 thousand. The assessment of occupational exposure to crystalline silica comprises several steps: primarily workplace determinations, quantitative sample analyses and comparisons of the obtained results with admissible values. This work describes a set of instruments that enables direct comparison of the study results with admissible values binding in almost 40 countries. It also highlights the consequences resulting from the classification of quartz and cristobalite, the most common forms of crystalline silica, as carcinogens by the International Agency for Research on Cancer (IARC). A survey of air sampling and dust determination methods used in various countries to measure airborne dust concentrations of crystalline silica in occupational environments are presented along with relevant tables. The GESTIS data base, specifying the methods considered by EU as suitable for measuring and assessing harmful agents, was used as the selection criterion. Particular attention was paid to the methods used to determine crystalline silica; the effect of analytical methods applied, sample preparation procedures, and reference materials on the results of determinations was also analyzed. Main parameters of method validation, such as detection and determination limits, and precision of the analysis were compared.

[Analysis of the competences of workplace inspecting laboratories for the determination of free crystalline silica (FCS), based on proficiency testing results]. / Analiza kompetencji laboratoriów badan srodowiska pracy do prowadzenia oznaczen wolnej krystalicznej krzemionki (WKK), na podstawie wyników badania bieglosci.

BACKGROUND: The aim of the study was to evaluate and analyze the technical competences of workplace inspection laboratories for the determination of free crystalline silica (FCS). MATERIAL AND METHODS: The study was based on the results of two series of control determinations carried out under the proficiency testing scheme in 2005 and the outcome of the questionnaire on analytical details and the quality system of laboratories. The mean values of proficiency indicies and the frequency of the obtained satisfactory performances were adopted as the basis of laboratory competences comparisons. RESULTS AND CONCLUSIONS: In total, 138 laboratories participated in the study, including 104 laboratories covered by one series and 34 by both series of determinations. Satisfactory technical competences were found in 77% of laboratories, regardless of their type and analytical methods applied. It was shown that the positive proficiency appraisal was linked with the regular application of quality control methods, i.e. internal control of FCS determination quality, the participation in laboratory proficiency testing and laboratory accreditation. The analytical equipment and mode of determining crystalline silica with use of the chemical method had no significant effect on the analytical performance.

[Exposure to silica dust in the Polish construction industry]. / Ocena narazenia pracowników budowlanych na pyl zawierajacy wolni krystaliczna krzemionke (WKK).

BACKGROUND: In the construction industry, free crystalline silica (FCS), mostly in the form of quartz, is in a very common use. Construction, especially repair and demolition works, are associated with emission of considerable amounts of FCS-containing dusts. Studies concerning the work environment, carried out recently in other countries, indicate that exposure to quartz frequently exceeds hygiene standards, i.e. safety limits for workers' health. The aim of this study was to assess dust exposure of workers employed at selected workposts in the construction industry in Poland. MATERIAL AND METHODS: The Polish study was performed in a group of workers employed in large and small enterprises and involved in establishing new constructions and demolishing old buildings. The group comprised 43 workers, employed at 9 workposts, who underwent 107 measurements of dust concentrations, of which 78 measurements were included in the analysis. At each workpost, concentrations of inhalable and respirable dusts were measured with the filtration and gravimetric method. Individual dust dosimeters were used to collect air samples and infrared spectrometry to determine concentrations of FCS dusts in samples of inhalable and respirable dusts. An identification analysis of dust samples was performed with use of X-ray diffraction. RESULTS: The results of the study show that geometric means of inhalable dust concentrations fell within a wide range from 2.1 (concrete mixer operator, plasterer) to 66.0 mg/m3 (laborer engaged in hand demolition), and those of respirable dust at the same workposts ranged from 0.4 to 16.2 mg/m3, respectively. Quartz was present in the majority of construction materials applied, and its concentration in inhalable dusts ranged from 7 to 13 mg/m3. CONCLUSIONS: It was found that dust concentrations exceeded hygiene standards at most of the workposts. Particularly high concentrations were observed at the workposts of surface abrasive grinders-coat finishers and workers engaged in drilling and hammering wholes. In conclusion, the need to use technical means, primarily personal respiratory protectors, to reduce dust concentrations should be strongly stressed.

[Free crystalline silica: a comparison of methods for its determination in total dust]. / Wolna krystaliczna krzemionka (WKK) - porównanie metod jej oznaczania w pytach catkowitych.

BACKGROUND: The major objective of the study was to compare and investigate the usefulness of quantitative analyses of free crystalline silica (FCS) in the assessment of dust exposure in samples of total dust of varied composition, using three methods: chemical method in common use in Poland; infrared spectrometry; and x-ray powder diffraction. MATERIALS AND METHODS: Mineral composition and FCS contents were investigated in 9 laboratory samples of raw materials, materials, and industrial wastes, containing from about 2 to over 80% of crystalline silica and reduced to particles of size corresponding with that of total dust. Sample components were identified using XRD and FT-IR methods. Ten independent determinations of FCS with each of the three study methods were performed in dust samples. An analysis of linear correlation was applied to investigate interrelationship between mean FCS determinations. RESULTS: In analyzed dust samples, along with silica dust there were numerous minerals interfering with silica during the quantitative analysis. Comparison of mean results of FCS determinations showed that the results obtained using the FT-IR method were by 12-13% lower than those obtained with two other methods. However, the differences observed were within the limits of changeability of results associated with their precision and dependence on reference materials used. CONCLUSIONS: Assessment of occupational exposure to dusts containing crystalline silica can be performed on the basis of quantitative analysis of FCS in total dusts using each of the compared methods. The FT-IR method is most appropriate for the FCS determination in samples of small amount of silica or collected at low dust concentrations; the XRD method for the analysis of multicomponent samples; and the chemical method in the case of medium and high FCS contents in samples or high concentrations of dusts in the work environment.