transmembrane pressure
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BACKGROUND: Photodynamic therapy (PDT) is linked with oxidative damage of biomolecules causing significant impairment of essential cellular functions that lead to cell death. It is the reason why photodynamic therapy has found application in treatment of different oncological, cardiovascular, skin and eye diseases. Efficacy of PDT depends on combined action of three components; sensitizer, light and oxygen. In the present study, we examined whether higher partial pressure of oxygen increases lethality in HeLa cell lines exposed to light in the presence of chloraluminium phthalocyanine disulfonate (ClAlPcS2). METHODS: ClAlPcS2- sensitized HeLa cells incubated under different oxygen conditions were exposed to PDT. Production of singlet oxygen ((1)O2) and other forms of reactive oxygen species (ROS) as well as changes in mitochondrial membrane potential were determined by appropriately sensitive fluorescence probes. The effect of PDT on HeLa cell viability under different oxygen conditions was quantified using the standard methylthiazol tetrazolium (MTT) test. RESULTS: At the highest oxygen concentration of 28 ± 2 mg/l HeLa cells were significantly more sensitive to light-activated ClAlPcS2 (EC50=0.29 ± 0.05 μM) in comparison to cells incubated at lower oxygen concentrations of 8 ± 0.5 and 0.5 ± 0.1 mg/l, where the half maximal effective concentration was 0.42 ± 0.06 μM and 0.94 ± 0.14 μM, respectively. Moreover, we found that the higher presence of oxygen is accompanied with higher production of singlet oxygen, a higher rate of type II photodynamic reactions, and a significant drop in the mitochondrial membrane potential. CONCLUSION: These results demonstrate that the photodynamic effect in cervical cancer cells utilizing ClAlPcS2 significantly depends on oxygen level.
- MeSH
- fotochemoterapie * MeSH
- fotosenzibilizující látky farmakologie MeSH
- HeLa buňky MeSH
- indoly farmakologie MeSH
- kyslík analýza farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- parciální tlak MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The application of negative pressure of -40 kPa (-300 mm Hg) for 10 min under a suction electrode placed on the surface of the spontaneously beating frog ventricle changed the extracellular potassium activity (aoK+) in three phases: a phase of rapidly rising aoK+, a slowly decaying phase and a phase of slowly rising aoK+. The changes reversed when suction was discontinued during the rapidly rising and decaying phase, but were not reversed during the slowly rising phase. Calcium extra-cellular activity (aoCa2+) decreased between -5 and -13 kPa, but increased during the higher pressures. The results indicated that injury of the ventricular tissue caused by a suction electrode elevated aoK+ and altered aoCa2+.
- MeSH
- akční potenciály MeSH
- decerebrační rigidita MeSH
- draslík fyziologie MeSH
- elektrody MeSH
- extracelulární prostor fyziologie MeSH
- membránové potenciály MeSH
- odsávání * MeSH
- Rana temporaria MeSH
- reakční čas MeSH
- srdce fyziologie MeSH
- srdeční komory MeSH
- vápník fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Východisko. U pacientů s chronickou atrioventrikulární blokádou (AVB) nebo prostou komorovou kardiostimulací (VVI) a zachovanou sinusovou depolarizací jsou levá a pravá předsíň (LA, RA) přetížené zvýšeným intraatriálním tlakem způsobeným atrioventrikulární dyssynchronií (AVDys). Přetížené síně mohou dilatovat a ztratit svou kontraktilní funkci. Cílem práce bylo zjistit vztah mezi intrakardiálně měřeným tlakem a dilatací předsíní u pacientů s AVDys a současně také ověřit, zda případná dilatace pravé předsíně u těchto pacientů souvisí s nižším elektrickým potenciálem pravé síně. Metody. U 26 pacientů (77 ± 10 let, 16 mužů), kde dlouhodobá AVDys byla hlavním patofyziologickým mechanismem vedoucím k přetížení síní (12 AVB, 14 VVI), byly změřeny intrakardiální tlaky (žilní, pravokomorový, plicní arteriální a zaklíněný – PWP) a elektrické potenciály v pravé síni. Tyto veličiny korelovaly s echokardiograficky získanými parametry (rozměry, objemy a ejekční frakce levé a pravé síně). Výsledky. Ejekční frakce LA a PWP vykazovaly středně silnou inversní korelaci: r = –0,489, p = 0,025, hladina významnosti 0,05. Souvislost PWP a morfologických ukazatelů LA nebyla potvrzena. Nebyly nalezeny významné korelace mezi intraatriálním potenciálem RA a její morfologií či funkcí. Ani pravostranné tlaky nekorelovaly s echokardiografickými ukazateli. Závěry. Ve studovaném souboru byla nalezena inverzní korelace mezi zaklíněným tlakem a ejekční frakcí levé síně, nepodařilo se však prokázat jinou korelaci morfologických a funkčních parametrů předsíní měřených echokardiograficky s intrakardiálním tlakem ani elektrickým potenciálem.
Background: In pts with chronic complete heart block or single chamber pacing and preserved sinus depolarization, left and right atria (LA, RA) may suffer from increased intraatrial pressure resulting from atrioventricular dyssynchrony (AVDys), dilate and lose their contractile function. Purpose: To find out whether any correlation exists between the echocardiographicaly measured LA, RA morphological and functional parameters on one hand and the intracardiac RA pressures and electrical potentials on the other hand in patients with chronic AVDys. Methods: In 26 pts (77 ±10 yrs., 16 males), where a chronic AVDys was the most important patophysiological mechanism of atrial overloading, the intraatrial pressures (atrial, right ventricular, pulmonary arterial and wedge pressure /PWP/) and electrical potentials (upper, middle, lower part of RA and RA appendage) were correlated with atrial diameters, volumes, ejection fraction and filling parameters. Results: There was a moderate inverse correlation between the LA ejection fraction and PWP: r = - 0,489, p = 0,025 at a level of significance 0.05), but no relationship between PWP and LA size/volumes. No correlation between RA potentials or intracardiac pressures and RA morphologic or functional features were documented. Conclusions: In this study, an inverse correlation between the capillary wedge pressure and left atrial ejection fraction in pts with chronic atrioventricular dyssynchrony was documented.
- Klíčová slova
- předsíně, morfologie, intrakardiální tlak,
- MeSH
- atrioventrikulární blokáda patofyziologie MeSH
- dilatace patologická MeSH
- echokardiografie statistika a číselné údaje MeSH
- hemodynamika fyziologie MeSH
- kardiostimulace umělá MeSH
- krevní tlak MeSH
- lidé MeSH
- membránové potenciály MeSH
- senioři MeSH
- srdce - funkce síní MeSH
- srdeční síně patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
Essential hypertension is a multifactorial disorder which belongs to the main risk factors responsible for renal and cardiovascular complications. This review is focused on the experimental research of neural and vascular mechanisms involved in the high blood pressure control. The attention is paid to the abnormalities in the regulation of sympathetic nervous system activity and adrenoceptor alterations as well as the changes of membrane and intracellular processes in the vascular smooth muscle cells of spontaneously hypertensive rats. These abnormalities lead to increased vascular tone arising from altered regulation of calcium influx through L-VDCC channels, which has a crucial role for excitation-contraction coupling, as well as for so-called "calcium sensitization" mediated by the RhoA/Rho-kinase pathway. Regulation of both pathways is dependent on the complex interplay of various vasodilator and vasoconstrictor stimuli. Two major antagonistic players in the regulation of blood pressure, i.e. sympathetic nervous system (by stimulation of adrenoceptors coupled to stimulatory and inhibitory G proteins) and nitric oxide (by cGMP signaling pathway), elicit their actions via the control of calcium influx through L-VDCC. However, L-type calcium current can also be regulated by the changes in membrane potential elicited by the activation of potassium channels, the impaired function of which was detected in hypertensive animals. The dominant role of enhanced calcium influx in the pathogenesis of high blood pressure of genetically hypertensive animals is confirmed not only by therapeutic efficacy of calcium antagonists but especially by the absence of hypertension in animals in which L-type calcium current was diminished by pertussis toxin-induced inactivation of inhibitory G proteins. Although there is considerable information on the complex neural and vascular alterations in rats with established hypertension, the detailed description of their appearance during the induction of hypertension is still missing.
- MeSH
- adrenergní receptory fyziologie MeSH
- cévní endotel patofyziologie MeSH
- guanosinmonofosfát cyklický metabolismus MeSH
- hypertenze metabolismus patofyziologie MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- membránové potenciály MeSH
- svaly hladké cévní fyziologie MeSH
- sympatický nervový systém patofyziologie MeSH
- vápník metabolismus MeSH
- vápníkové kanály - typ L metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Five pathogenic Candida species were compared in terms of their osmotolerance, tolerance to toxic sodium and lithium cations, and resistance to fluconazole. The species not only differed, in general, in their tolerance to high osmotic pressure (C. albicans and C. parapsilosis being the most osmotolerant) but exhibited distinct sensitivities to toxic sodium and lithium cations, with C. parapsilosis and C. tropicalis being very tolerant but C. krusei and C. dubliniensis sensitive to LiCl. The treatment of both fluconazole-susceptible (C. albicans and C. parapsilosis) and fluconazole-resistant (C. dubliniensis, C. krusei and C. tropicalis) growing cells with subinhibitory concentrations of fluconazole resulted in substantially elevated intracellular Na(+) levels. Using a diS-C3(3) assay, for the first time, to monitor the relative membrane potential (ΔΨ) of Candida cells, we show that the fluconazole treatment of growing cells of all five species results in a substantial hyperpolarization of their plasma membranes, which is responsible for an increased non-specific transport of toxic alkali metal cations and other cationic drugs (e.g., hygromycin B). Thus, the combination of relatively low doses of fluconazole and drugs, whose import into the tested Candida strains is driven by the cell membrane potential, might be especially potent in terms of its ability to inhibit the growth of or even kill various Candida species.
- MeSH
- antifungální látky farmakologie MeSH
- buněčná membrána účinky léků fyziologie MeSH
- Candida účinky léků MeSH
- cytosol chemie MeSH
- flukonazol farmakologie MeSH
- lithium toxicita MeSH
- membránové potenciály účinky léků MeSH
- osmotický tlak MeSH
- sodík toxicita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Composite membranes containing molecular sieve particles embedded in a polyimide matrix are promising due to their increased permeability and high selectivity in gas separation processes. Determination of permeability of dense membranes is time-consuming and the resulting values are loaded with experimental errors. The impact of uncertainty in various quantities on the reliability of the permeability values measured by the constant volume/ variable pressure method was analyzed. The total uncertainty of the measurements on polyimide/Silicalite-1 membranes is 7–13 %, the errors in membrane thickness and permeation coefficient being the main contributing factors.
Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.
- MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky farmakologie MeSH
- HeLa buňky MeSH
- indoly aplikace a dávkování farmakologie MeSH
- kyslík aplikace a dávkování farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- metaloporfyriny aplikace a dávkování farmakologie MeSH
- mitochondrie účinky léků MeSH
- organokovové sloučeniny aplikace a dávkování farmakologie MeSH
- parciální tlak MeSH
- singletový kyslík analýza MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins. By deriving a generalized form for the Nernst equation, we find that a relatively small magnetic field (approximately 1 T) with a large gradient (up to 1 GT/m) can significantly change the membrane potential of the cell and thus have a significant impact on not only the properties and biological functionality of cells but also cell fate.
