The vertical growth rate of basaltic magma chambers remains largely unknown with available estimates being highly uncertain. Here, we propose a novel approach to address this issue using the classical Skaergaard intrusion that started crystallizing from all margins inward only after it had been completely filled with magma. Our numerical simulations indicate that to keep the growing Skaergaard magma chamber completely molten, the vertical growth rate must have been on the order of several hundreds to a few thousands of meters per year, corresponding to volumetric flow rates of tens to hundreds of cubic kilometers per year. These rates are several orders of magnitude higher than current estimates and were likely achieved by rapid subsidence of the floor rocks along faults. We propose that the Skaergaard is a plutonic equivalent of supereruptions or intrusions that grow via catastrophically rapid magma emplacement into the crust, producing totally molten magma chambers in a matter of a few months to dozens of years.

• Publikační typ
• časopisecké články MeSH

Endodontic treatment of immature permanent teeth with necrotic pulp poses several clinical challenges and is one of the most demanding interventions in endodontics. Recently, with new discoveries in the field of tissue engineering, novel treatment protocols have been established. The most promising treatment modality is revascularization, whose integral part is the exposure of collagen matrix and embedded growth factors. However, optimization of the treatment protocol requires a development of analytical procedures able to analyze growth factors directly on the sample surface. In this work, method based on surface-enhanced Raman spectroscopy (SERS) was developed to investigate the influence of the time of the medical treatment using EDTA on exposure and accessibility of the growth factors, namely TGF-ß1, BMP-2, and bFGF on the dentine surface. The nanotags, which consist of magnetic Fe3O4@Ag nanocomposite covalently functionalized by tagged antibodies (anti-TGF-ß1-Cy3, anti-BMP-2-Cy5, and anti-bFGF-Cy7), were employed as a SERS substrate. Each antibody was coupled with a unique label allowing us to perform a parallel analysis of all three growth factors within one analytical run. Developed methodology presents an interesting alternative to a fluorescence microscopy and in contrary allows evaluating a chemical composition and thus minimizing possible false-positive results. Graphical abstract.

• MeSH
• dentin chemie   MeSH
• fibroblastový růstový faktor 2 analýza   MeSH
• kavita zubní dřeně chemie   MeSH
• kostní morfogenetický protein 2 analýza   MeSH
• lidé MeSH
• nanokompozity chemie   MeSH
• oxid železnato-železitý chemie   MeSH
• Ramanova spektroskopie metody   MeSH
• stříbro chemie   MeSH
• transformující růstový faktor beta analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is characterized by abnormal proliferation of corneal endothelial cells. It was shown that TGF-β2 present in aqueous humor (AH) could help maintaining the corneal endothelium in a G1-phase-arrest state. We wanted to determine whether the levels of this protein are changed in AH of PPCD patients. METHODS: We determined the concentrations of active TGF-β2 in the AH of 29 PPCD patients (42 samples) and 40 cadaver controls (44 samples) by ELISA. For data analysis the PPCD patients were divided based on either the molecular genetic cause of their disease as PPCD1 (37 samples), PPCD3 (1 sample) and PPCDx (not linked to a known PPCD loci, 4 samples) or on the presence (17 samples) or absence (25 samples) of secondary glaucoma or on whether they had undergone penetrating keratoplasty (PK, 32 samples) or repeated PK (rePK, 7 samples). RESULTS: The level of active TGF-β2 in the AH of all PPCD patients (mean ± SD; 386.98 ± 114.88 pg/ml) in comparison to the control group (260.95 ± 112.43 pg/ml) was significantly higher (P = 0.0001). Compared to the control group, a significantly higher level of active TGF-β2 was found in the PPCD1 (P = 0.0005) and PPCDx (P = 0.0022) groups. Among patients the levels of active TGF-β2 were not significantly affected by gender, age, secondary glaucoma or by the progression of dystrophy when one or repeated PK were performed. CONCLUSION: The levels of active TGF-β2 in the AH of PPCD patients are significantly higher than control values, and thus the increased levels of TGF-β2 could be a consequence of the PPCD phenotype and can be considered as another feature characterizing this disease.

• MeSH
• dědičné dystrofie rohovky metabolismus   MeSH
• glaukom metabolismus   MeSH
• keratoplastika perforující metody   MeSH
• komorová voda metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rohovka metabolismus   MeSH
• rohovkový endotel metabolismus   MeSH
• transformující růstový faktor beta2 metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• monitorování plodu MeSH
• nemoci plodu ultrasonografie   MeSH
• ultrasonografie prenatální MeSH
• vrozené vady ultrasonografie   vrozené   MeSH
• vývoj plodu MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• chemie, klinická chemie
• gynekologie a porodnictví
• gynekologie a porodnictví

Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.

• MeSH
• ampicilin farmakologie   MeSH
• anaerobní bakterie MeSH
• antibakteriální látky farmakologie   MeSH
• Bacteria MeSH
• Escherichia coli MeSH
• hyperbarická oxygenace * MeSH
• Klebsiella pneumoniae MeSH
• kombinace léků trimethoprim a sulfamethoxazol farmakologie   MeSH
• kyslík MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• oxidační stres MeSH
• pseudomonádové infekce * MeSH
• Pseudomonas aeruginosa MeSH
• sulbaktam MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Since ovarian cancer cells express CD44, which causes very strong cell adhesion to peritoneal mesothelium and an unfavourable prognosis, we designed small interfering RNA (siRNA) targeting the CD44 gene to analyse the functional consequences of this inhibition in human ovarian cancer. We transfected ovarian cancer cell line SKOV-3 with well-designed CD44 siRNA or control siRNA. Western blot analysis was used to assess the CD44 expression. Following stable transfection, significant inhibition of CD44 expression with 66.13 +/- 4.21 % (P < 0.05) in CD44 siRNA1 cells and 62.01 +/- 3.97 % (P < 0.05) in CD44 siRNA2 cells was detected. We performed in vitro experiments including cellular adhesion to hyaluronan and human peritoneal mesothelial cells, etoposide-induced apoptosis, and Boyden chamber invasion assays. The adhesion percentages of CD44 siRNA1 and CD44 siRNA2 cells were significantly lower than those of the control siRNA cells in adhesion both to hyaluronan and to human peritoneal mesothelium. The CD44 siRNA transfectants showed significant inhibition of in vitro invasion and loss of resistance to apoptosis than the control siRNA cells. In vivo study with BALB/c mice was applied to compare the tumour growth and peritoneal dissemination. Nude mice treated with CD44 siRNA cells revealed significantly lower tumour volume and less peritoneal dissemination compared to mice treated with the control siRNA cells. In conclusion, downregulation of CD44 expression by siRNA inhibits the in vitro adhesion, invasion and resistance to apoptosis of ovarian cancer cells, suppresses tumour growth and peritoneal dissemination of human ovarian cancer xenograft in nude mice.

• MeSH
• antigeny CD44 genetika   MeSH
• apoptóza genetika   imunologie   MeSH
• buněčná adheze genetika   MeSH
• down regulace genetika   imunologie   MeSH
• exprese genu MeSH
• genetická terapie MeSH
• kyselina hyaluronová metabolismus   MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• metastázy nádorů MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků genetika   patologie   MeSH
• RNA interference MeSH
• transfekce MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

BACKGROUND: Autologous dermal fibroblasts may be useful in the treatment of skin wounds and for the enhancement of keratinocyte proliferation. This paper addressed the following questions: (1) can cultured fibroblasts (CF) be transplanted as suspensions to full-thickness skin wounds and do they influence wound healing; (2) will the transplanted CF be integrated into the new dermis; (3) can a transgene that encodes a secretable marker, human epidermal growth factor (hEGF), be expressed in the wound fluid by the transplanted CF; and (4) do CF cotransplanted with cultured keratinocytes (CK) influence the rate of wound healing? METHODS: Suspensions of CF were transplanted alone or together with CK to full-thickness wounds covered with liquid-containing chambers in an established porcine model. RESULTS: Transplantation of CF accelerated reepithelialization as determined from wound histologies and sequential measurements of protein efflux over the wound surface. CF transfected with a marker gene, beta-galactosidase, resulted in in vivo gene expression and demonstrated that transplanted CF integrated into the developing dermis. Transplantation of hEGF gene-transfected CF resulted in significant hEGF expression in wound fluid. The hEGF levels peaked at day 1 (2450 pg/ml) and then sharply decreased to low levels on day 6. CF cotransplanted with CK led to greater number of keratinocyte colonies in the wound and accelerated reepithelialization as compared with CK alone. CONCLUSIONS: Transplanted CF integrated into the dermis, accelerated reepithelialization, and improved the outcome of CK transplantation. CF may also be used for the expression of transgenes in wound and wound fluid.

• MeSH
• autologní transplantace MeSH
• epidermální růstový faktor fyziologie   MeSH
• fibroblasty transplantace   MeSH
• hojení ran * MeSH
• keratinocyty transplantace   MeSH
• kultivované buňky MeSH
• kůže cytologie   MeSH
• prasata MeSH
• suspenze MeSH
• transgeny MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

• MeSH
• dědičné dystrofie rohovky * diagnóza   etiologie   genetika   patologie   MeSH
• exony genetika   MeSH
• genetické testování * metody   využití   MeSH
• introny genetika   MeSH
• lidé MeSH
• mutace MeSH
• prospektivní studie MeSH
• rohovkový endotel patologie   MeSH
• sekvenční analýza MeSH
• transformující růstový faktor beta1 diagnostické užití   MeSH
• úbytek endoteliálních buněk rohovky genetika   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH
• Spojené království MeSH

The extract from milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin, contains a variety of flavonolignans and displays antioxidant, anti-inflammatory, immunomodulatory and hepatoprotective properties. As silybin is the main component of silymarin, the literature mainly focuses on this compound, ignoring all other components. This leads to problems in reproducibility of scientific results, as the exact composition of silymarin is often unknown and can vary to a certain degree depending on the processing, chemo-variety of the plant used and climatic conditions during the plant growth. There are studies dealing with the analytical separation and quantification of silymarin components as well as studies focused on silymarin content in clinically used drugs, in various plant parts, seasons, geographic locations etc. However, no comparison of detail flavonolignan profiles in various silymarin preparations is available to date. Also, as a result of the focus on the flavonolignans; the oil fraction, which contains linoleic, oleic and palmitic acids, sterols, tocopherol (vitamin E) and phospholipids, has been neglected. Due to all these factors, the whole plant is used e.g. as animal feed, the leaves can be eaten in salads and seed oil, besides culinary uses, can be also utilized for biodiesel or polymer production. Various HPLC separation techniques for the determination of the content of the flavonolignans have been vastly summarized in the present review.

• MeSH
• antiflogistika analýza   chemie   MeSH
• antioxidancia analýza   chemie   MeSH
• flavonolignany analýza   chemie   MeSH
• imunologické faktory analýza   chemie   MeSH
• rostlinné extrakty analýza   chemie   MeSH
• semena rostlinná chemie   MeSH
• silibinin analýza   chemie   MeSH
• silymarin analýza   chemie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Ciel: Zistiť efekt opakovaných intravitreálnych aplikácii afliberceptu na endotel rohovky u pacientov s diabetickým makulárnym edémom (DME) a edémom makuly pri oklúzii retinálnej vény (RVO). Metodika: Do prospektívneho sledovania v období od januára 2021 do novembra 2023 bolo zaradených 87 naivných očí s diagnózou DME a RVO. Exklúzne kritérium pre zaradenie bol operačný alebo laserový zákrok počas sledovacieho obdobia, nosenie kontaktných šošoviek, ope rácia katarakty pred menej ako 6 mesiacmi, dystrofie alebo iné ochorenia rohovky, ktoré môžu spôsobiť zmeny endotelu. Okrem rutinných vyšetrení sme v deň 1., 4. a 8. injekcie vyšetrovali aj endotel rohovky pomocou bezkontaktnej endotelovej mikroskopie. Vyhodnocovali sme 4 parametre: hustotu endotelových buniek (CD), hexagonalitu (HEX), koeficient variability (CV) a centrálnu hrúbku rohovky (CCT). Najskôr sme vyhodnocovali celý súbor očí a následne sme ho rozdelili podľa 2 kritérií; podľa diagnózy na DME/RVO a podľa šošovky na fakické/pseu dofakické oči. Výsledky: Vyhodnotených bolo 87 očí (68 pacientov). Priemerný vek pacientov v čase diagnózy bol 66,8 ±9,3 rokov. Z celkového počtu 87 bolo 51 (59 %) fakických a 36 (41 %) pseudofakických očí. S diagnózou DME bolo liečených 61 (70 %) očí a s diagnózou RVO 26 (30 %). V prie behu sledovania nedošlo vplyvom liečby k štatisticky signifikantnej zmene priemerných hodnôt CD, HEX, CV, CCT či už v súbore všetkých očí alebo v rozdelení do podskupín podľa diagnózy či stavu šošovky. Záver: Zistili sme, že intravitreálne aplikácie afliberceptu u pacientov s DME a RVO neovplyvňujú parametre rohovkového endotelu ako CCT, HEX, CD, CV hodnotené pomocou endotelovej mikroskopie pri sledovaní po 8 injekciu.

Aim: To determine the effect of repeated intravitreal injections of aflibercept on the corneal endothelium in patients with diabetic macular edema (DME) and macular edema due to retinal vein occlusion (RVO). Methods: In a prospective study conducted between January 2021 and November 2023, a total of 87 treatment-naive eyes with DME and RVO were evaluated. The exclusion criteria were surgery or laser intervention during the follow-up period, contact lens wear, cataract surgery in the last 6 months, dystrophy, or other corneal condition that may cause endothelial damage. In addition to routine examinations on the day of application, we also measured the corneal endothelium using specular microscopy on the 1st, 4th and 8th day of injection. We evaluated 4 parameters: endothelial cell density (CD), hexagonality (HEX), coefficient of variability (CV) and central corneal thickness (CCT). First of all, we evaluated the entire cohort of eyes, and then divided it according to 2 criteria; the diagnosis into DME/RVO and according to the lens status into phakic/pseudophakic eyes. Results: A total of 87 eyes of 68 patients were evaluated. The average age of the patients at the time of diagnosis was 66.8 ±9.3 years. Within the cohort 51 (59%) eyes were phakic and 36 (41%) pseudophakic. A total of 61 (70%) eyes with a diagnosis of DME were treated, and 26 (30%) with RVO. During the follow-up, there were no significant changes in the average values of CD, HEX, CV, CCT due to aflibercept treatment, either in the whole group or in subgroups according to diagnosis or lens condition. Conclusions: The results of this study suggest that intravitreal administration of aflibercept in patients with DME and RVO did not have an impact on corneal endothelial parameters, including CCT, HEX, CD and CV. These parameters were measured using endothelial microscopy during an 8-injection observation period.

• Klíčová slova
• aflibercept,
• MeSH
• bevacizumab aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• endoteliální buňky účinky léků   MeSH
• humanizované monoklonální protilátky farmakologie   klasifikace   terapeutické užití   MeSH
• inhibitory angiogeneze * aplikace a dávkování   farmakologie   klasifikace   terapeutické užití   MeSH
• injekce intravitreální * klasifikace   metody   MeSH
• lidé MeSH
• makulární edém chemicky indukované   etiologie   MeSH
• mikroskopie klasifikace   metody   MeSH
• počet buněk MeSH
• prospektivní studie MeSH
• rohovkový endotel diagnostické zobrazování   účinky léků   MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH