Monitoring nitrate reduction: hydrogeochemistry and clogging potential in raw water wells.

The mainly agricultural input of NO3- and compliance with drinking water guideline values pose major challenges for many water suppliers. Additionally, associated changes in hydrochemistry, especially concerning products of NO3- reduction (Fe2+/3+, Mn2+/4+, Ca2+, Mg2+, SO42-, HCO3-) and subsequent reactions, can have a major influence on mineral saturation states and well yield: well productivity can be strongly reduced by mineral precipitation and silting. To evaluate hydrogeochemical evolution and clogging potential for a given well field, thorough hydrochemical and geochemical investigations are required. Therefore, time-dependent and depth-specific ion concentrations in water samples (n = 818) were analysed in a catchment area of a waterworks in western Germany. The sediments of the aquifers were extensively investigated for their geochemistry (CS, scanning electron microscope, aqua regia digestion and dithionite solution; n = 253). In addition, PhreeqC was used to model saturation indices in order to identify possible mineral precipitation in the wells. Results show a high NO3- input into deep wells screened in Tertiary sediments due to an admixture of Quaternary groundwater. Directly at the Quaternary-Tertiary boundary, chemolithotrophic NO3- reduction consuming pyrite occurs. Protons released during the process are pH-buffered by dissolving carbonate minerals. Overall, the hydrochemistry and especially the saturation indices are strongly influenced by NO3- reduction and its degradation products. A change in well yield has not yet been observed, but future clogging by ochre formation or sintering cannot be excluded.

Testis transcriptome alterations in zebrafish (Danio rerio) with reduced fertility due to developmental exposure to 17α-ethinyl estradiol.

17α-Ethinylestradiol (EE2) is a ubiquitous aquatic contaminant shown to decrease fish fertility at low concentrations, especially in fish exposed during development. The mechanisms of the decreased fertility are not fully understood. In this study, we perform transcriptome analysis by RNA sequencing of testes from zebrafish with previously reported lowered fertility due to exposure to low concentrations of EE2 during development. Fish were exposed to 1.2 and 1.6 ng/L (measured concentration; nominal concentrations 3 and 10 ng/L) of EE2 from fertilization to 80 days of age, followed by 82 days of remediation in clean water. RNA sequencing analysis revealed 249 and 16 genes to be differentially expressed after exposure to 1.2 and 1.6 ng/L, respectively; a larger inter-sample variation was noted in the latter. Expression of 11 genes were altered by both exposures and in the same direction. The coding sequences most affected could be categorized to the putative functions cell signalling, proteolysis, protein metabolic transport and lipid metabolic process. Several homeobox transcription factors involved in development and differentiation showed increased expression in response to EE2 and differential expression of genes related to cell death, differentiation and proliferation was observed. In addition, several genes related to steroid synthesis, testis development and function were differentially expressed. A number of genes associated with spermatogenesis in zebrafish and/or mouse were also found to be differentially expressed. Further, differences in non-coding sequences were observed, among them several differentially expressed miRNA that might contribute to testis gene regulation at post-transcriptional level. This study has generated insights of changes in gene expression that accompany fertility alterations in zebrafish males that persist after developmental exposure to environmental relevant concentrations of EE2 that persist followed by clean water to adulthood. Hopefully, this will generate hypotheses to test in search for mechanistic explanations.

[The analysis of the effectiveness of the combined treatment of the patients presenting with laryngeal papillomatosis]. / Analiz éffektivnosti kombinirovannogo lecheniia bol'nykh papillomatozom gortani.

The objective of the present work was to evaluate the effectiveness of the application of the inducer of endogenous interferon synthesis in the course of the combined treatment of the adult patients presenting with laryngeal papillomatosis. A total of 50 patients with this pathology were admitted and examined at the ENT Clinics of I.M. Sechenov First Moscow State Medical University and M.F. Vladimirsky Moscow Regional Research Clinical Institute during 24 months. The patients comprising group 1 (n=25) were treated with the use of cold plasma surgery and the inducer of endogenous interferon synthesis while those included in group 2 (n=25) received only surgical treatment. It was shown that the combined treatment including the surgical step (cold plasma surgery) followed by the treatment with the inducer of endogenous interferon synthesis to prevent relapses makes it possible to reduce the number of secondary surgical interventions, increase the duration of the intervals between relapses, and decrease the content of types 6 and 11 human papilloma virus in the saliva.

[Neurologic disturbances in children with cleft lip and cleft palate]. / Nevrologicheskie narusheniya u detei s rasshchelinoi guby i neba.

AIM: Neurological symptoms of genetic syndromes, including congenital cleft lip and palate (CLP) are well-studied while neurological characteristics of patients with non-syndromal CLP are not described. The authors studied neurological disturbances in CLP. MATERIAL AND METHODS: Twenty-one patients with CLP, mean age 12.0±4.7 years (the main group) were compared to healthy people (the control group). RESULTS AND CONCLUSION: Elements of bulbar syndrome (atrophy and deviation of the tongue, sagging of the soft palate, specific speech disturbances) and mimic innervation abnormalities (hypomimia or hypermimia, face asymmetry), microfocal neurological symptoms occurred significantly more frequently (p<0.01) in patients of the main group. Bulbar disorders, identified in 100% of the patients, were most characteristic of CLP. The neurological features of patients with CLP demonstrate the involvement of the brain stem, mimic innervation, bulbar cranial nerves and defects of the development of the neural tube.

Identification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening.

The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and docking strategies, as well as the ligand-based pharmacophore model. High-throughput screening of the resulting compound sets in a biochemical kinase inhibition assay allowed us to identify several novel chemotypes that represent attractive starting points for the development of advanced IGF1R inhibitory compounds.

[Tongue structure, position and function in cleft lip and palate children assessed by ultrasound examination].

The aim of the study was to examine the position and function of the tongue in cleft lip and palate (CLP) patients and to reveal their impact on alveolar bone development. Two hundred and fifty-eight CLP children and 50 healthy children as control group were included in the study. Tongue function and position were assessed by ultrasound examination. In CLP patients the dorsum of the tongue was deformed and the asymmetry of some tongue structures was also found out (mainly the massive of the tongue muscles). Low tip and high dorsum position were specific for CLP children as well as discoordinated tongue movements. Both in static and dynamic condition the tongue was pressed to the lower alveolar bone thus disturbing its development. The obtained data showed tongue position and function to be one of the causes for lower promacrognathy and lingual inclination of incisors in CLP patients. The absence of tongue impact on the upper alveolar bone should be seen as one of the factors for upper retromicrognathy.

Novel fluorescent trimethine cyanine dye 7519 for amyloid fibril inhibition assay.

Fluorescence spectroscopy was used to study the ability of dye 7519 to follow the transition of monomeric insulin into fibrils and applicability of the dye to the insulin aggregation inhibition assay. The commercially available classic amyloid stain, thioflavin T, was used as the reference dye. For selecting potential inhibitors, the QSAR approach was applied. Dye 7519 appeared to be suitable for monitoring insulin aggregation into fibrils in vitro. The properties of the dye allowed us to test it as a potential probe in the screening assay of potential inhibitors of insulin fibrillization. One hundred forty-four flavonoids were tested as potential inhibitors of amyloid fibril formation using the quantitative structure activity relationship approach. Among them, 10 candidates with high indexes of inhibition were selected for tests in vitro using dye 7519 and the reference amyloid dye thioflavine T. Using dye 7519 fluorescence, we found that two compounds had inhibitory effects on insulin amyloid formation. These results agree with inhibition data using the thioflavine T assay. Our studies demonstrated that the fluorescent cyanine dye 7519 is a sensitive probe for quantitative detection of insulin amyloid formation and can be applied to screen agents capable of affecting aggregation of amyloid proteins.

Explorations of the application of cyanine dyes for quantitative alpha-synuclein detection.

We examined the practical aspects of using fluorescent mono (T-284) and trimethinecyanine (SH-516) dyes for detecting and quantifying fibrillar alpha-synuclein (ASN). We studied the interaction of cyanine dyes with fibrillar proteins using fluorescence spectroscopy and atomic force microscopy. The commercially available classic amyloid stain thioflavin T (Thio T) was used as the reference dye. T-284 and SH-516 dyes can be used for fluorometric quantification of fibrillar wild-type ASN at concentrations of approximately 1.5-20 microg/ml. Both dyes appeared suitable for step-wise monitoring of ASN variants (wild-type and mutants A30P and A53T) aggregation into fibrils in vitro, demonstrating good reproducibility, exceeding that for the commonly used Thio T. Our assay may be used for screening in vitro of agents capable of affecting the aggregation of ASN. In addition, T-284 and SH-516 cyanine dyes were shown to recognize amyloid proteins of various amino acid compositions selectively. T-284 demonstrated particular sensitivity to wild-type and A53T ASN, while for SH 516, the fluorescence response to fibrillar proteins was nearly the same except for lysozymes. T-284 and SH-516 cyanine dyes are sensitive and specific fluorescent probes for monitoring ASN fibril formation process in vitro, quantification of fibrillar ASN in solution, and fluorescent detection of various fibrillar protein species.

Specific fluorescent detection of fibrillar alpha-synuclein using mono- and trimethine cyanine dyes.

With the aim of searching of novel amyloid-specific fluorescent probes the ability of series of mono- and trimethine cyanines based on benzothiazole, pyridine and quinoline heterocycle end groups to recognize fibrillar formations of alpha-synuclein (ASN) was studied. For the first time it was revealed that monomethine cyanines can specifically increase their fluorescence in aggregated ASN presence. Dialkylamino-substituted monomethine cyanine T-284 and meso-ethyl-substituted trimethine cyanine SH-516 demonstrated the higher emission intensity and selectivity to aggregated ASN than classic amyloid stain Thioflavin T, and could be proposed as novel efficient fluorescent probes for fibrillar ASN detection. Studies of structure-function dependences have shown that incorporation of amino- or diethylamino- substituents into the 6-position of the benzothiazole heterocycle yields in a appearance of a selective fluorescent response to fibrillar alpha-synuclein presence. Performed calculations of molecular dimensions of studied cyanine dyes gave us the possibility to presume, that dyes bind with their long axes parallel to the fibril axis via insertion into the neat rows (so called 'channels') running along fibril.

Cyanine dye-protein interactions: looking for fluorescent probes for amyloid structures.

We ascertained the ability to detect fibrillar beta-lactoglobulin (BLG) of a series of mono-, tri-, penta-, and heptamethinecyanines based on benzothiazole and benzimidazole heterocycles, and of benzothiazole squaraine. Fluorescence properties of these cyanine dyes were measured in the unbound state and in the presence of monomeric and fibrillar BLG and compared with those for the commercially available benzothiazole dye Thioflavin T. The correlation between the chemical nature of the dye molecules and the ability of dyes to bind aggregated proteins was established. We found that meso-substituted cyanines with amino substituents in heterocycle in contrast to the corresponding unsubstituted dyes have a binding preference to fibrillar BLG and a noticeable fluorescence response in the presence of the aggregated protein. For the squaraines and benzimidazole penthamethinecyanines studied, fluorescence emission increased both in the presence of native and fibrillar protein. The trimethinecyanines T-49 and SH-516 exhibit specifically increased fluorescence in the presence of fibrillar BLG. These dyes demonstrated the same or higher emission intensity and selectivity to aggregated BLG as Thioflavin T, and are proposed for application in selective fluorescent detection of aggregated proteins.

Fluorescent properties of pentamethine cyanine dyes with cyclopentene and cyclohexene group in presence of biological molecules.

A series of pentamethine cyanine dyes with cyclohexene or cyclopentene group in polymethyne chain, assumed as DNA groove-binders, were studied as fluorescent probes for nucleic acids as well as for native and denatured proteins. It was revealed that the presence of methyl or dimethyl substituent in 5 position of the cyclohexene group hinders the formation of dye-DNA fluorescent complex, while the methyl substituent in 2 position leads to the increasing of the dye-DNA complex fluorescence intensity. The dyes SL-251, SL-1041, and SL-1046 containing methyl group in the 2 position of the cyclic group, are reported as bright DNA-sensitive dyes. The study of the dyes DNA-binding specificity demonstrated significant AT-preference that points to the groove-binding interaction mode. At the same time, the dyes SL-251, SL-377, and SL-957 with the 2-methyl substituted cyclohexene group were shown to be sensitive fluorescent dyes both for nonspecific (in SDS presence) proteins detection and for native BSA.

[Post-tuberculous fibrous mediastinitis: a report of a case followed-up for many years]. / Posttuberkuleznyi fibroziruiushchii mediastinit (analiz mnogoletnego nabliudeniia).

The paper reports a rare case of fibrosing mediastinitis of posttuberculous genesis caused by infection with Mycobacterium bovis. Such cases are not available in the literature so far. The patient was observed from 1956 to 2001. Bovine tubercle bacilla affect mediastinal lymph nodes which undergo fibrosis resulting in stenosis of the trachea, major bronchi, esophagus. Narrowing of the chest duct leads to formation of severe recurrent transudate in the left pleural cavity (for 3 years 70 pleural punctures were made with removal of a total of 22 l of fluid).

[Stage I-III pulmonary sarcoidosis complicated by nephrogenic (vasopressin-resistant) form of diabetes insipidus]. / Sarkoidoz lëgkikh III stadii, oslozhnennyi nefrogennoi (vazopressin-rezistentnoi) formoi nesakharnogo diabeta.

Literature data and original experience of the authors with 6890 cases of respiratory sarcoidosis (stage I-III) suggest that diabetes ipsipidus in respiratory sarcoidosis (RS) can present as hypothalamic-hypophysial form (observed at the stage I-II by physicians since 1935) and a new form--nephrogenic (vasopressin-resistant) at stage II of pulmonary sarcoidosis. The latter form is little known. It was found that in stage III sarcoidosis patients who have severe fibrosis of the lungs and a long history of corticosteroid hormone treatment the nephrogenic form of the pathogenesis is caused by defects in calcium metabolism leading to nephrocalcinosis with low sensitivity of renal tubular receptors to ADH. Adiurecrine treatment is unefficient. It is recommended to use chlorpropamide which raises sensitivity of the tubules to ADH.

[Genetic markers of the ABO blood system in pulmonary sarcoidosis patients of different ethnic origin]. / Geneticheskie markery krovi sistemy ABO u bol'nykh sarkoidozom legkikh v zavisimosti ot etnicheskoi prinadlezhnosti.

Analysis of published data and investigations of their own permitted the authors to detect the relationship between the incidence of AB0 blood groups and the ethnic appurtenance. The 0(1) and A(II) blood groups were appreciably more incident in the Europeans, including the Russians, whereas in the Asians (Kazakhs et al.) the B(III) group prevailed. In the Russian sarcoidosis patients groups A(II), less frequently B(III) predominated. The clinical course of sarcoidosis is more benign in patients with the 0(I) group, the initial and first stages of the disease predominating. In patients with the A(II) group sarcoidosis runs an unfavorable course, with the second and third stages predominating, and hence, patients with this blood group should be singled out as the risk group.