BACKGROUND: The current generation of neonatal ventilators enables periodic storage of set, measured, and calculated ventilatory parameters. DESIGN: Retrospective observational study. OBJECTIVES: To evaluate and identify the ventilatory, demographic, and clinical pre-extubation variables that are significant for estimating extubation readiness. METHODS: Eligible subjects included premature infants <33 weeks of gestation weaned from mechanical ventilation (MV) lasting >24 h. A total of 16 relevant ventilator variables, each calculated from 288 data points over 24 h, together with eight demographic and three clinical pre-extubation variables, were used to create the generalized linear model (GLM) for a binary outcome and the Cox proportional hazards model for time-to-event analysis. The achievement of a 120-h period without reintubation was defined as a successful extubation attempt (EA) within the binary outcome. RESULTS: We evaluated 149 EAs in 81 infants with a median (interquartile range) gestational age of 25+2 (24+3-26+1) weeks. Of this, 90 EAs (60%) were successful while 59 (40%) failed. GLM identified dynamic compliance per kilogram, percentage of spontaneous minute ventilation, and postmenstrual age as significant independent positive variables. Conversely, dynamic compliance variability emerged as a significant independent negative variable for extubation success. This model enabled the creation of a probability estimator for extubation success with a good proportion of sensitivity and specificity (80% and 73% for a cut-off of 60%, respectively). CONCLUSIONS: Ventilator variables reflecting lung mechanical properties and the ability to spontaneously breathe during MV contribute to better prediction of extubation readiness in extremely premature infants with chronic lung disease.

• MeSH
• extubace * MeSH
• gestační stáří MeSH
• lidé MeSH
• mechanické ventilátory MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• odpojení od ventilátoru * metody   MeSH
• retrospektivní studie MeSH
• umělé dýchání * metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Příspěvek obsahuje český překlad doporučení European consensus guidelines on the management of respiratory distress syndrome ohledně používání oxygenoterapie u nezralých novorozenců, doplněný o nové patofyziologické poznatky, na jejichž základě může v budoucnu dojít k úpravě a individualizaci používání oxygenoterapie podle gestačního stáří pacienta.

The following text is a Czech translation of the European consensus guidelines on the management of respiratory distress syndrome recommendations on oxygenotherapy in preterm infants, supplemented by emerging pathophysiological findings, which might necessitate an updated version of these recommendations to be released, stratified by gestational age.

• Klíčová slova
• postmenstruační věk,
• MeSH
• lidé MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• oxygenoterapie metody   MeSH
• saturace kyslíkem * MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH

The antiproliferative and antitumor effect of leaf ribonuclease was tested in vitro on the human ML-2 tumor cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease in vitro studies was negligible. In the experiments in vivo a significant decrease of the tumor size, however was observed. From nucleases the mung bean nuclease (PhA) was studied first from nucleases. The antitumor effect of this enzyme on ML2 human tumor cell line was almost non-effective. However, significant antitumor activity was detected on human melanoma tumors in vivo. The antitumor effect of black pine pollen nuclease (PN) tested in vitro was also negligible. On the other side, in the experiments in vivo a significant decrease of the human melanoma tumor size was observed too. Recombinant plant nucleases of tomato (TBN1) and hop (HBN1) (submitted to patenting under no. PV 2008-384;Z7585) were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant both nucleases were as effective against human melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about ten times lower concentrations compared to the use of bovine seminal RNase (BS-RNase).

• MeSH
• endonukleasy farmakologie   terapeutické užití   MeSH
• lidé MeSH
• melanom farmakoterapie   patologie   MeSH
• myši nahé MeSH
• myši MeSH
• proliferace buněk účinky léků   MeSH
• ribonukleasy farmakologie   terapeutické užití   MeSH
• rostlinné proteiny farmakologie   terapeutické užití   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Recombinant plant nucleases R-TBN1 and R-HBN1 were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant nucleases were as effective against melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about 10 times lower concentrations compared to the use of bovine seminal RNase (BS-RNase). Because the recombinant nucleases R-HBN1 and R-TBN1 share only 67.4% amino acid identity and showed only partial immunochemical cross-reactivity, their similar anticancerogenic effects can be mainly explained by their catalytical similarity. Both recombinant nucleases showed lower degree of aspermatogenesis compared to BS-RNAse and PN nuclease. Unlike BS-RNase, aspermatogenesis induced by both recombinant nucleases could not be prevented by the homologous antibody complexes. Owing to relatively low cytotoxicity on the one hand, and high efficiency at low protein levels on the other, recombinant plant nucleases R-HBN1 and R-TBN1 appear to be stable biochemical agents that can be targeted as potential antitumor cytostatics.

• MeSH
• endonukleasy farmakologie   genetika   MeSH
• glykosylace MeSH
• Humulus enzymologie   MeSH
• lidé MeSH
• melanom enzymologie   patologie   prevence a kontrola   MeSH
• myeloidní leukemie enzymologie   patologie   prevence a kontrola   MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• proliferace buněk MeSH
• protinádorové látky farmakologie   MeSH
• rekombinantní proteiny farmakologie   genetika   MeSH
• skot MeSH
• Solanum lycopersicum enzymologie   MeSH
• spermatogeneze MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The antitumor effect of black pine (Pinus nigra) pollen nuclease (PN) tested in vitro was negligible in comparison with bovine seminal ribonuclease (BS-RNase). However, in the experiments in vivo a significant decrease of the human melanoma tumor size was observed in the mice treated with this nuclease and also with the animal RNases and DNase I. In nude mice injected intratumoraly with PN (10 microg/dose) the tumor size decreased from 100% in the control mice to 46% in treated mice whereas in counterparts treated with BS-RNase and DNase I the tumor growth was reduced a little more, however after ten times higher doses (100 and 80 microg per dose). Certain aspermatogenic and embryotoxic activity as an expression of side effects of PN and comparative enzymes also appeared, but it was lower compared to the effect of bovine seminal ribonuclease. Immunogenicity of PN was significantly weaker in comparison with BS-RNase. The antibodies against black pine nuclease produced in the injected mice did not inactivate the biological effects of this plant nuclease in vivo. In conclusion PN nuclease proved in vivo higher antitumor activity against human melanoma tumors growing in athymic mice in comparison with animal bovine seminal ribonuclease and DNase I.

• MeSH
• borovice enzymologie   MeSH
• embryonální vývoj účinky léků   MeSH
• endonukleasy farmakologie   imunologie   toxicita   MeSH
• endoribonukleasy farmakologie   MeSH
• financování organizované MeSH
• fytogenní protinádorové látky farmakologie   MeSH
• lidé MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pyl enzymologie   MeSH
• spermatogeneze účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

Polyspermine-ribonuclease A (PS-RNase A) and polyspermine-dimeric ribonuclease A (PS-dimeric RNase A) were prepared by cross-linking ribonuclease A or its covalently linked dimer to polyspermine (PS) using dimethyl suberimidate. The two RNase A derivatives were tested for a possible antitumor action. The in vitro and in vivo cytotoxic activity of PS-RNase A, although strong, is not higher than that known for free polyspermine. PS-dimeric RNase A, which was characterized by mass spectroscopy, titration of free amine groups, and enzymatic assays, proved instead to be a definitely more efficient antitumor agent, both in vitro and in vivo. This result could tentatively be explained in view of the importance of positive charges for ribonuclease activity, considering the higher basicity of PS-dimeric RNase A compared to that of PS-(monomeric)RNase A. It must be also taken into account that the dimeric RNase A moiety of PS-dimeric RNase A could evade the cytoplasmic ribonuclease inhibitor, which instead could trap the monomeric RNase A moiety of the other derivative. The two RNase A derivatives degrade poly(A).poly(U) under conditions where native RNase A is inactive. The results of this work demonstrate once again the importance of positive charges for the functions of mammalian pancreatic type ribonucleases in general, in particular for RNase A derivatives, and the potential therapeutic use of the ribonuclease A derivatives.

• MeSH
• dimerizace MeSH
• financování organizované MeSH
• gelová chromatografie MeSH
• kultivované buňky MeSH
• lidé MeSH
• molekulární struktura MeSH
• pankreatická ribonukleasa MeSH
• proliferace buněk účinky léků   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• RNA metabolismus   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• spermin chemie   MeSH
• Check Tag
• lidé MeSH

A significant aspermatogenic activity, ascertained by microscopic studies of seminiferous tubules and interstitial tissue, and by the observation of the entrance of immunity and fibrocytic cells in mice injected with polyspermine (PS) or polyspermine conjugated to monomeric or dimeric RNase A (PS-RNase A or PS-dimeric RNase A, respectively), was found either in mice injected or in non-injected testes. Polyspermine and its complexes with RNase A destroyed all spermatogenic and intertestitial tissue, including Leydic cells, as well as their ability to secrete testosterone. The total loss of spermatogenic activity in injected testes is irreversible because spermatogonia cells also were destroyed. The injection of PS into both mice testes determined the total degeneration of testicle tissue in 50% of injected testes. The second half of testes was also partly degenerated, and if they were re-injected, almost all testes were fully destroyed. PS-dimeric RNase A injected once into both testicles produced a stronger degeneration and also the interruption of testosterone secretion in comparison with the effects due to injection of mice with PS or PS-RNase A. In all mice treated with these substances, as well as in rats in which PS was injected twice into their testes, we detected polymorfonucleates, monocytes, plasma cells, lymphocytes.and fibrocytic cells. Antibodies against PS, PS-RNase A or PS-dimeric RNase A did not influence the aspermatogenic activity. Animals in which a repeated intra-peritoneal injection was carried out did not lose body mass and remained in good condition, with the exception of mice injected with spermine.

• MeSH
• antispermatogenní látky farmakologie   MeSH
• buňky imunologie   patologie   účinky léků   MeSH
• financování organizované využití   MeSH
• interpretace statistických dat MeSH
• myši inbrední ICR MeSH
• potkani Wistar MeSH
• ribonukleasy genetika   imunologie   účinky léků   MeSH
• spermatogeneze genetika   imunologie   účinky léků   MeSH
• spermin farmakologie   škodlivé účinky   MeSH
• testis imunologie   patologie   účinky léků   MeSH

The antiproliferative and antitumor effect of wheat leaf ribonuclease was tested in vitro on the human ML-2 cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease was negligible in comparison with bovine seminal ribonuclease. In the experiments in vivo, a significant decrease of the tumor size, however, was observed in the mice treated with wheat leaf ribonuclease (27 kDa) compared with the control RNase A and polyethylene glycol. In nude mice injected intratumoraly with wheat leaf ribonuclease, the tumor size decreased from 100% in the control mice to 39% in treated mice. In the mice treated with polyethylene glycol-conjugated wheat leaf ribonuclease, the tumor reduction was observed from 100 to 28%, whereas in counterparts treated with polyethylene glycol-conjugated bovine seminal ribonuclease the tumor inhibition was reduced from 100 to 33%. Certain aspermatogenic and embryotoxic activity of wheat leaf ribonuclease and bovine seminal ribonuclease also appeared, but was lower in comparison with the effect of onconase. Mutual immunological cross-reactivity between wheat leaf ribonuclease antigens on one side and animal RNases (bovine seminal ribonuclease, RNase A, human HP-RNase and onconase) on the other side proved a certain structural similarity between animal and plant ribonucleases. Immunogenicity of wheat leaf ribonuclease was weaker in comparison with bovine seminal ribonuclease (titer of antibodies 160-320 against 1280-2560 in bovine seminal ribonuclease). Interestingly, immunosuppressive effect of wheat leaf ribonuclease tested on mixed lymphocyte culture-stimulated human lymphocytes reached the same level as that of bovine seminal RNase. The antibodies against wheat leaf ribonuclease produced in the injected mice did not inactivate the biological effect of this plant RNase in vivo. This is probably the first paper in which plant ribonuclease was used as antiproliferative and antitumor drug against animal and human normal and tumor cells and tissues in comparison with animal ribonucleases.

• MeSH
• embryo savčí účinky léků   MeSH
• financování organizované MeSH
• fytogenní protinádorové látky izolace a purifikace   terapeutické užití   toxicita   MeSH
• imunosupresiva MeSH
• injekce intraperitoneální MeSH
• lidé MeSH
• listy rostlin chemie   MeSH
• lymfocyty imunologie   účinky léků   MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   terapie   MeSH
• polyethylenglykoly MeSH
• proliferace buněk účinky léků   MeSH
• pšenice enzymologie   MeSH
• ribonukleasy MeSH
• spermatogeneze účinky léků   MeSH
• těhotenství MeSH
• testis patologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH

Previously we have shown that monomeric RNase A has no significant biological activity, whereas its oligomers (dimer to tetramer) prepared by lyophilizing from 50% acetic acid solutions, show remarkable aspermatogenic and antitumor activities. Furthermore, conjugates prepared by chemical binding of native RNase A to polyethylene glycol (PEG) have shown a significant aspermatogenic and antitumor activities. In this work we show that the chemical conjugation of PEG to the RNase A C-dimer, and to the two RNase A trimers (NC-trimer and C- trimer) decreases the aspermatogenic activity of the oligomers while increasing their inhibitory activity on the growth of the human UB900518 amelanotic melanoma transplanted in athymic nude mice. Moreover, the PEG-conjugated RNaseA oligomers are devoid, like the free oligomers, of any embryotoxic activity.

• MeSH
• antispermatogenní látky farmakologie   MeSH
• dimerizace MeSH
• embryo savčí účinky léků   MeSH
• lidé MeSH
• melanom experimentální farmakoterapie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pankreatická ribonukleasa farmakologie   chemie   MeSH
• peptidové fragmenty farmakologie   chemie   MeSH
• polyethylenglykoly farmakologie   chemie   MeSH
• protinádorové látky farmakologie   chemie   MeSH
• spermatogeneze účinky léků   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• antispermatogenní látky farmakologie   MeSH
• embryo savčí účinky léků   MeSH
• endonukleasy specifické pro jednořetězcové nukleové kyseliny * farmakologie   imunologie   MeSH
• experimentální nádory * farmakoterapie   MeSH
• fazol * enzymologie   MeSH
• lidé MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pankreatická ribonukleasa farmakologie   imunologie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• spermatogeneze účinky léků   MeSH
• spermie účinky léků   MeSH
• teratogeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH