Sostoyanie trombotsitarnogo gemostaza u detey s sakharnym diabetom

Цель. Провести эпидемиологическую характеристику сахарного диабетиа 1 типа у детей и подростков Калининградского региона. Материалы и методы. Регистр детей в Калининградском регионе создавался с использованием методики и диагностических критериев, рекомендованных Интернациональной группой по изучению эпидемиологии сахарного диабета. Для создания регистра и оценки степени полноты составления регистра использовались два источника информации. Все дети с впервые выявленным сахарным диабетом госпитализируются в эндокринологическое отделение Детской областной больницы г. Калининграда. В дальнейшем дети находятся на учете в районных поликлиниках, где они получают инсулин. Информация о больных СД 1 типа детях из стационара больницы считается первичным источником информации. Результаты. Начиная с 1989 г, заболеваемость СД 1 типа неуклонно нарастает, при незначительных ежегодных колебаниях. В 1989-1993 гг. уровень заболеваемости колебался от 1,977 до 3,625 на 100 тыс. детского населения, составляя в среднем 2,926. В период с 1994 по 1999 г. уровень заболеваемости колебался от 4,177 до 8,550, составляя в среднем 6,095 на 100 тыс. детского населения. В 2000-2002 гг. заболеваемость составляла 8,460-12,716, в среднем ? 10,752. Таким образом, за 13 лет заболеваемость СД 1 типа в Калининградском регионе увеличилась в среднем в 3,7 раза; ежегодный прирост заболеваемости составил в среднем 8,5%. Распространенность СД 1 типа неуклонно возрастает (11,04 в 1989 г. и 78,30 в 2002 г.). В наибольшей степени этот процесс был выражен в последние 2 года. Выводы. Заболеваемость СД 1 типа у детей Калининградского региона за 13 лет увеличилась в 4 раза и превышает средний показатель заболеваемости по России. Девочки болеют в 1,4 раза чаще, чем мальчики. В последние годы заболеваемость СД 1 типа среди детей области выше, чем среди детей, проживающих в Калининграде. Распространенность СД 1 типа в Калининградском регионе в 1,4 раза выше, чем в среднем по России, и приближается к уровню распространенности в скандинавских странах. Высокая заболеваемость и распространенность СД 1 типа отмечается в основном в семьях ?старых? мигрантов

The Metabolite Profiling of <i>Aspergillus fumigatus</i> KMM4631 and Its Co-Cultures with Other Marine Fungi

An Aspergillus fumigatus KMM 4631 strain was previously isolated from a Pacific soft coral Sinularia sp. sample and was found to be a source of a number of bioactive secondary metabolites. The aims of this work are the confirmation of this strain’ identification based on ITS, BenA, CaM, and RPB2 regions/gene sequences and the investigation of secondary metabolite profiles of Aspergillus fumigatus KMM 4631 culture and its co-cultures with Penicillium hispanicum KMM 4689, Amphichorda sp. KMM 4639, Penicillium sp. KMM 4672, and Asteromyces cruciatus KMM 4696 from the Collection of Marine Microorganisms (PIBOC FEB RAS, Vladivostok, Russia). Moreover, the DPPH-radical scavenging activity, urease inhibition, and cytotoxicity of joint fungal cultures’ extracts on HepG2 cells were tested. The detailed UPLC MS qTOF investigation resulted in the identification and annotation of indolediketopiperazine, quinazoline, and tryptoquivaline-related alkaloids as well as a number of polyketides (totally 20 compounds) in the extract of Aspergillus fumigatus KMM 4631. The metabolite profiles of the co-cultures of A. fumigatus with Penicillium hispanicum, Penicillium sp., and Amphichorda sp. were similar to those of Penicillium hispanicum, Penicillium sp., and Amphichorda sp. monocultures. The metabolite profile of the co-culture of A. fumigatus with Asteromyces cruciatus differed from that of each monoculture and may be more promising for the isolation of new compounds

Sargassopenillines A–G, 6,6-Spiroketals from the Alga-Derived Fungi Penicillium thomii and Penicillium lividum

Seven new 6,6-spiroketals, sargassopenillines A–G (1–7) were isolated from the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. The structures of these metabolites were determined by HR-MS and 1D and 2D NMR. The absolute configurations of compounds 1, 5 and 6 were assigned by the modified Mosher’s method and by CD data. Sargassopenilline C (3) inhibited the transcriptional activity of the oncogenic nuclear factor AP-1 with an IC50 value of 15 µM

A Study of the Metabolic Profiles of <i>Penicillium dimorphosporum</i> KMM 4689 Which Led to Its Re-Identification as <i>Penicillium hispanicum</i>

Changes in cultivation conditions, in particular salinity and temperature, affect the production of secondary fungal metabolites. In this work, the extracts of fungus previously described as Penicillium dimorphosporum cultivated in various salinity and temperature conditions were investigated using HPLC UV/MS techniques, and their DPPH radical scavenging and cytotoxicity activities against human prostate cancer PC-3 cells and rat cardiomyocytes H9c2 were tested. In total, 25 compounds, including 13 desoxyisoaustamide-related alkaloids and eight anthraquinones, were identified in the studied extracts and their relative amounts were estimated. The production of known neuroprotective alkaloids 5, 6 and other brevianamide alkaloids was increased in hypersaline and high-temperature conditions, and this may be an adaptation to extreme conditions. On the other hand, hyposalinity stress may induce the synthesis of unidentified antioxidants with low cytotoxicity that could be very interesting for future investigation. The study of secondary metabolites of the strain KMM 4689 showed that although brevianamide-related alkaloids and anthraquinone pigments are widely distributed in various fungi, these metabolites have not been described for P. dimorphosporum and related species. For this reason, the strain KMM 4689 was re-sequenced using the β-tubulin gene and ITS regions as molecular markers and further identified as P. hispanicum

Metabolite profiles of Paragliomastix luzulae (formerly named as Acremonium striatisporum) KMM 4401 and its co-cultures with Penicillium hispanicum KMM 4689

Abstract The marine holothurian-derived fungal strain KMM 4401 has been identified as Paragliomastix luzulae using 28S rDNA, ITS regions and the partial TEF1 gene sequences. The metabolite profile of the fungal culture was studied by UPLC-MS technique. The strain KMM 4401 is a source of various virescenoside-type isopimarane glycosides suggested as chemotaxonomic feature for this fungal species. Also Px. luzulae KMM 4401 was proposed as possible source of new bioactive secondary metabolites especially antimicrobials. Moreover, the co-cultures of Px. luzulae KMM 4401 with another marine fungus Penicillium hispanicum KMM 4689 inoculated simultaneously or after two weeks were investigated by same way. It was shown, that P. hispanicum KMM 4689 suppressed the production of most of Px. luzulae KMM 4401 metabolites. On the other hand, the co-cultivation of P. hispanicum KMM 4689 and Px. luzulae KMM 4401 resulted in increasing of production of main deoxyisoaustamide alkaloids of P. hispanicum KMM 4689 on 50–190%. Graphical Abstrac

New Cyclopiane Diterpenes and Polyketide Derivatives from Marine Sediment-Derived Fungus <i>Penicillium antarcticum</i> KMM 4670 and Their Biological Activities

Two new cyclopiane diterpenes and a new cladosporin precursor, together with four known related compounds, were isolated from the marine sediment-derived fungus Penicillium antarcticum KMM 4670, which was re-identified based on phylogenetic inference from ITS, BenA, CaM, and RPB2 gene regions. The absolute stereostructures of the isolated cyclopianes were determined using modified Mosher’s method and quantum chemical calculations of the ECD spectra. The isolation from the natural source of two biosynthetic precursors of cladosporin from a natural source has been reported for the first time. The antimicrobial activities of the isolated compounds against Staphylococcus aureus, Escherichia coli, and Candida albicans as well as the inhibition of staphylococcal sortase A activity were investigated. Moreover, the cytotoxicity of the compounds to mammalian cardiomyocytes H9c2 was studied. As a result, new cyclopiane diterpene 13-epi-conidiogenone F was found to be a sortase A inhibitor and a promising anti-staphylococcal agent

Meroterpenoids from the Alga-Derived Fungi <i>Penicillium thomii</i> Maire and <i>Penicillium lividum</i> Westling

Ten new austalide meroterpenoids (<b>1</b>–<b>10</b>) were isolated from the alga-derived fungi <i>Penicillium thomii</i> KMM 4645 and <i>Penicillium lividum</i> KMM 4663. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The absolute configurations of some of the metabolites were assigned by the modified Mosher’s method and CD data. Compounds <b>1</b>, <b>2</b>, <b>8</b>, and <b>9</b> were able to inhibit AP-1-dependent transcriptional activity in JB6 Cl41 cell lines at noncytotoxic concentrations. Austalides <b>1</b>–<b>5</b>, <b>8</b>, and <b>9</b> exhibited significant inhibitory activity against <i>endo</i>-1,3-β-d-glucanase from a crystalline stalk of the marine mollusk <i>Pseudocardium sachalinensis</i>

New Zosteropenillines and Pallidopenillines from the Seagrass-Derived Fungus <i>Penicillium yezoense</i> KMM 4679

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher’s method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1–14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC50 of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer

Anthraquinone Derivatives and Other Aromatic Compounds from Marine Fungus <i>Asteromyces cruciatus</i> KMM 4696 and Their Effects against <i>Staphylococcus aureus</i>

New anthraquinone derivatives acruciquinones A–C (1–3), together with ten known metabolites, were isolated from the obligate marine fungus Asteromyces cruciatus KMM 4696. Acruciquinone C is the first member of anthraquinone derivatives with a 6/6/5 backbone. The structures of isolated compounds were established based on NMR and MS data. The absolute stereoconfigurations of new acruciquinones A–C were determined using ECD and quantum chemical calculations (TDDFT approach). A plausible biosynthetic pathway of the novel acruciquinone C was proposed. Compounds 1–4 and 6–13 showed a significant antimicrobial effects against Staphylococcus aureus growth, and acruciquinone A (1), dendryol B (4), coniothyrinone B (7), and ω-hydroxypachybasin (9) reduced the activity of a key staphylococcal enzyme, sortase A. Moreover, the compounds, excluding 4, inhibited urease activity. We studied the effects of anthraquinones 1, 4, 7, and 9 and coniothyrinone D (6) in an in vitro model of skin infection when HaCaT keratinocytes were cocultivated with S. aureus. Anthraquinones significantly reduce the negative impact of S. aureus on the viability, migration, and proliferation of infected HaCaT keratinocytes, and acruciquinone A (1) revealed the most pronounced effect

New piperazine derivatives helvamides B–C from the marine-derived fungus Penicillium velutinum ZK-14 uncovered by OSMAC (One Strain Many Compounds) strategy

Abstract Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed. Graphical Abstrac