Elevated Hydrostatic Pressure Research Articles

Brittle tectonothermal evolution in the Forsmark area, central Fennoscandian Shield, recorded by paragenesis, orientation and 40Ar/ 39Ar geochronology of fracture minerals

In this paper, we show how studies of fracture mineral paragenesis, their orientation and 40Ar/ 39Ar geochronology can be applied in order to recognise the brittle tectonothermal evolution in an area. Samples were selected from nearly 18 km of drill cores from the upper 1 km of the Fennoscandian Shield obtained during the site investigation for a repository of spent nuclear fuel in Forsmark, central Sweden. Four major events of fracturing and/or reactivation of fractures associated with fracture mineralisation have been distinguished. The first event was characterised by precipitation of epidote, quartz and chlorite, along preferably sub-horizontal and gently-dipping fractures or steep, WNW–ESE to NW–SE fractures. Precipitation occurred between 1.8 and 1.1 Ga, possibly during the late stage of the Svecokarelian orogeny close to 1.8–1.7 Ga. The second event is associated with precipitation of hematite-stained adularia and albite, prehnite, laumontite, calcite and chlorite, preferably along steep, ENE–WSW to NNE–SSW and NNW–SSE fractures. Precipitation occurred around 1107 ± 7 to 1034 ± 3 Ma, probably due to effects from the Sveconorwegian orogeny. This event was followed by a period with dissolution of fracture minerals and subsequent precipitation of mainly calcite, quartz, pyrite and asphaltite during the Palaeozoic. The formation fluid emanated from an overlying organic-rich sedimentary cover. Precipitation occurred during reactivation of Proterozoic fractures, but formation of new fractures is also inferred, possibly due to far-field effects of the Caledonian orogeny, or elevated hydrostatic pressure due to its foreland basin. The latest event is dominated by clay minerals, chlorite and calcite along hydraulically conductive fractures. These minerals are prominent along sub-horizontal and gently-dipping fractures, but also occur in sets of steeply-dipping fractures. It is inferred that the hydraulically conductive fractures are Proterozoic structures in which mineral precipitation has occurred during a long period. However, some of the near-surface, sub-horizontal fractures may be Quaternary in age.

Mechanism and Related Kinetics of 5-Methyltetrahydrofolic Acid Degradation during Combined High Hydrostatic Pressure−Thermal Treatments

The mechanism and kinetics of the degradation of 5-methyltetrahydrofolic acid during thermal and combined high pressure-thermal treatments in an aqueous solution were investigated. In a first approach the degradation was described by a first-order kinetic model using single-response modeling, and the combined pressure-temperature dependence of the resulting degradation rate constants was empirically described. To obtain a mechanistic insight, degradation products were purified and identified by LC-MS and NMR. Quantification of an s-triazine derivative, 5-methyldihydrofolic acid, and p-aminobenzoyl-l-glutamate as predominant degradation products at atmospheric pressure resulted in elucidation and kinetic characterization of the folate degradation mechanism by Bayesian multiresponse modeling. The postulated mechanism was evaluated at elevated hydrostatic pressure. On the basis of the pressure and temperature dependence of the reaction rates, some degradation reactions were either accelerated or decelerated upon application of pressure. Multiresponse kinetics can be a valuable tool to assess the impact of high hydrostatic pressure and other processing techniques on nutrients, and incorporating mechanistic insights can advance the current kinetic approach for process optimization.

Common Evolution of Mechanical and Transport Properties in Thermally Cracked Westerly Granite at Elevated Hydrostatic Pressure

Increasing the damage and crack porosity in crustal rocks can result in significant changes to various key physical properties, including mechanical strength, elastic and mechanical anisotropy, and the enhancement of transport properties. Using a Non-Interactive Crack Effective Medium (NIC) theory as a fundamental tool, we show that elastic wave dispersion can be inverted to evaluate crack density as a function of temperature and is compared with optically determined crack density. Further, we show how the existence of embedded microcrack fabrics in rocks also significantly influences the fracture toughness (KIC) of rocks as measured via a suite of tensile failure experiments (chevron cracked notch Brazilian disk). Finally, we include fluid flow in our analysis via the Guéguen and Dienes crack porosity-permeability model. Using the crack density and aspect ratio recovered from the elastic-wave velocity inversion, we successfully compare permeability evolution with pressure with the laboratory measurements of permeability.

Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes

Optic nerve head astrocytes become abnormal in eyes that have elevated intraocular pressure, and cultured astrocytes display altered protein expression after being subjected for > or = 1 days to elevated hydrostatic pressure. Here we show that 2-h elevated hydrostatic pressure (15 or 30 mmHg) causes phosphorylation of ERK1/2, ribosomal S6 protein kinase (p90(RSK)), and Na/H exchanger (NHE)1 in cultured rat optic nerve head astrocytes as judged by Western blot analysis. The MEK/ERK inhibitor U0126 abolished phosphorylation of NHE1 and p90(RSK) as well as ERK1/2. To examine NHE1 activity, cytoplasmic pH (pH(i)) was measured with BCECF and, in some experiments, cells were acidified by 5-min exposure to 20 mM ammonium chloride. Although baseline pH(i) was unaltered, the rate of pH(i) recovery from acidification was fourfold higher in pressure-treated astrocytes. In the presence of either U0126 or dimethylamiloride (DMA), an NHE inhibitor, hydrostatic pressure did not change the rate of pH(i) recovery. The findings are consistent with NHE1 activation due to phosphorylation of ERK1/2, p90(RSK), and NHE1 that occurs in response to hydrostatic pressure. These responses may precede long-term changes of protein expression known to occur in pressure-stressed astrocytes.

Investigating the Role of Ischemia vs. Elevated Hydrostatic Pressure Associated with Acute Obstructive Uropathy

Obstructive uropathy can cause irreversible renal damage. It has been hypothesized that elevated hydrostatic pressure within renal tubules and/or renal ischemia contributes to cellular injury following obstruction. However, these assaults are essentially impossible to isolate in vivo. Therefore, we developed a novel pressure system to evaluate the isolated and coordinated effects of elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and (3) elevated pressure + ischemic insults. Cellular responses including cell density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)), were recorded after 24 h of insult and following recovery. Data were analyzed to assess the primary effects of ischemic insults and elevated pressure. Unlike pressure, ischemic insults exerted a primary effect on nearly all response measurements. We also evaluated the data for insult interactions and identified significant interactions between ischemic insults and pressure. Altogether, findings indicate that pressure may sub-lethally effect cells and alter cellular metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia may be the primary, but not the sole, cause of cellular injury induced by obstructive uropathy.

Elevated Hydrostatic Pressure Activates Sodium‐Hydrogen Exchanger‐1 in Rat Optic Nerve Head Astrocytes

ObjectiveOptic nerve head (ONH) astrocytes are thought to involve in the degeneration of ganglion cells and remodeling of surrounding extracellular matrix in glaucoma. Elevated intraocular pressure (IOP) is the main glaucoma risk factor. Here we report altered sodium hydrogen exchange (NHE) activity in cells exposed to elevated hydrostatic pressure .MethodsHydorstatic pressure (HP) of 15 mmHg was applied to the cells in a 20 cm glass cylinder filled with the culture medium equilibrated with 5% CO2/95% air for 2h. Proteins were analyzed by Western blot and cytoplasmic pH (pHi) was measured by BCECF ratiometry.ResultsElevated HP causes phosphorylation of ERK1/2, ribosomal S6 kinase (p90RSK), and Na‐H exchanger‐1 (NHE1). The MEK/ERK inhibitor UO126 abolished phosphorylation of NHE1 and p90RSK as well as ERK1/2. Although baseline pHi was unaltered in pressure treated cells, the rate of pHi recovery from ammonium chloride acidification was four fold higher. Dimethylamiloride (DMA), an NHE inhibitor, abolished and U0126 partially inhibited the increased rate of pHi recovery in pressure treated astrocytes.ConclusionsThe findings suggest elevated HP caused NHE‐1 activation through phosphorylation following activation of ERK1/2 and p90RSK. These events may lead to the long term changes of protein expression known to occur in pressure‐stressed astrocytes.FundingNIH Grant EY014069

Estimation of the cavitation peak pressure using the Na D-line structure in the sonoluminescence spectra

The sonoluminescence (SL) spectra of an Ar-saturated NaCl solution in the region of the Na D line excited by ultrasound at a frequency of 22 and 44 kHz have been measured at a solution temperature within 5–20°C and the normal and elevated hydrostatic pressure. Based on an analysis of the obtained results in comparison to published data, it is established that variations in the intensity and structure of the Na D line in the SL spectra of NaCl solutions are related to changes in the intensity of the so-called red satellite. Using the measured red satellite intensity, the peak pressure in the cavitation bubbles was estimated at 800–1200 bar depending on the experimental conditions.

Effect of pressure annealing on formation of light‐emitting Si nanocrystals in Si rich SiO2

AbstractFour types of Si rich SiO2 layers on the Si substrates have been prepared by Si ion implantation or by magnetron co‐sputtering of the Si and SiO2 targets. The types differed from each other in the contents of excess Si, which were about 5 at%, 15 at%, 25 at% and 35 at%. High temperature (up to 1100 °C) anneals of the samples were performed in neutral ambient under normal or elevated (up to 1.5 GPa) hydrostatic pressures. Photoluminescence spectroscopy, Raman scattering and electron diffraction were used for the characterizations. For the lowest concentration of the excess Si the high‐pressure annealing prevents the formation of the light‐emitting Si nanocrystals, but stimulates an appearance of the centers luminescing in the visible range. These centers are believed to be numerous Si nanoclusters, segregated from the oxide network. Increase in Si content provides during the high‐pressure anneals the formation of the quantum‐size Si nanocrystals able to emit strong PL near the wavelength of 800 nm. The effect of the high‐pressure annealing is ascribed to the enhanced energetically favorable segregation of Si from the oxide network. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

TRPV1: Contribution to Retinal Ganglion Cell Apoptosis and Increased Intracellular Ca2+with Exposure to Hydrostatic Pressure

Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to pressure sensing and Ca(2+)-dependent cell death in other systems, also contributes to pressure-induced RGC death and whether this contribution involves Ca(2+). trpv1 mRNA expression in RGCs was probed with the use of PCR and TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin) and agonism (capsaicin) were used to probe how TRPV1 activation affects the survival of isolated RGCs at ambient and elevated hydrostatic pressure (+70 mm Hg). Finally, for RGCs under pressure, the authors tested whether EGTA chelation of Ca(2+) improves survival and whether, with the Ca(2+) dye Fluo-4 AM, TRPV1 contributes to increased intracellular Ca(2+). RGCs express trpv1 mRNA, with robust TRPV1 protein localization to the cell body and axon. For isolated RGCs under pressure, TRPV1 antagonism increased cell density and reduced apoptosis to ambient levels (P <or= 0.05), whereas for RGCs at ambient pressure, TRPV1 agonism reduced density and increased apoptosis to levels for elevated pressure (P <or= 0.01). Chelation of extracellular Ca(2+) reduced RGC apoptosis at elevated pressure by nearly twofold (P <or= 0.01). Exposure to elevated hydrostatic pressure induced a fourfold increase in RGC intracellular Ca(2+) that was reduced by half with TRPV1 antagonism. Finally, in the DBA/2 mouse model of glaucoma, levels of TRPV1 in RGCs increased with elevated IOP. RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca(2+).

Allosteric Transitions in Cytochrome P450eryF Explored with Pressure-Perturbation Spectroscopy, Lifetime FRET, and a Novel Fluorescent Substrate, Fluorol-7GA

To establish a direct method for monitoring substrate binding in cytochrome P450eryF applicable at elevated hydrostatic pressures, we introduce a laser dye Fluorol-7GA (F7GA) as a novel fluorescent ligand. The high intensity of fluorescence and the reasonable resolution of the excitation band from the absorbance bands of P450 allowed us to establish highly sensitive binding assays compatible with pressure perturbation. The interactions of F7GA with P450eryF cause an ample spin shift revealing cooperative binding ( S50 = 8.2 +/- 1.3 microM; n = 2.3 +/- 0.1). Fluorescence resonance energy transfer (FRET) experiments suggest the presence of at least two substrate binding sites with apparent K D values in the ranges of 0.1-0.3 and 6-9 microM. Similar to that observed earlier with CYP3A4, increasing hydrostatic pressure does not cause either a complete dissociation of the substrate complexes or a displacement of the spin equilibrium toward the low-spin state. Rather, increased pressure enhances the cooperativity of the F7GA-induced spin shift, so that the Hill coefficient approaches 3 at 2 kbar. Lifetime FRET experiments revealed an important increase in the affinity of the enzyme for F7GA at elevated pressures, suggesting that the binding of the ligand induces a conformational transition associated with an important increase in the level of protein hydration. This transition largely attenuates the solvent accessibility of the heme pocket and causes an unusual stability of the high-spin, substrate-bound enzyme at elevated pressures.

Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment

The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place.

Cell proliferation at 122 degrees C and isotopically heavy CH4 production by a hyperthermophilic methanogen under high-pressure cultivation.

We have developed a technique for cultivation of chemolithoautotrophs under high hydrostatic pressures that is successfully applicable to various types of deep-sea chemolithoautotrophs, including methanogens. It is based on a glass-syringe-sealing liquid medium and gas mixture used in conjunction with a butyl rubber piston and a metallic needle stuck into butyl rubber. By using this technique, growth, survival, and methane production of a newly isolated, hyperthermophilic methanogen Methanopyrus kandleri strain 116 are characterized under high temperatures and hydrostatic pressures. Elevated hydrostatic pressures extend the temperature maximum for possible cell proliferation from 116 degrees C at 0.4 MPa to 122 degrees C at 20 MPa, providing the potential for growth even at 122 degrees C under an in situ high pressure. In addition, piezophilic growth significantly affected stable carbon isotope fractionation of methanogenesis from CO(2). Under conventional growth conditions, the isotope fractionation of methanogenesis by M. kandleri strain 116 was similar to values (-34 per thousand to -27 per thousand) previously reported for other hydrogenotrophic methanogens. However, under high hydrostatic pressures, the isotope fractionation effect became much smaller (< -12 per thousand), and the kinetic isotope effect at 122 degrees C and 40 MPa was -9.4 per thousand, which is one of the smallest effects ever reported. This observation will shed light on the sources and production mechanisms of deep-sea methane.

Xenon and Air Bubble Injection during Cardiopulmonary Bypass

Xenon and Air Bubble Injection during Cardiopulmonary Bypass

Contribution of TRPV1 to Microglia-Derived IL-6 and NFκB Translocation with Elevated Hydrostatic Pressure

The authors investigated the contributions of the transient receptor potential vanilloid-1 receptor (TRPV1) and Ca(2+) to microglial IL-6 and nuclear factor kappa B (NFkappaB) translocation with elevated hydrostatic pressure. The authors first examined IL-6 colocalization with the microglia marker Iba-1 in the DBA/2 mouse model of glaucoma to establish relevance. They isolated microglia from rat retina and maintained them at ambient or elevated (+70 mm Hg) hydrostatic pressure in vitro and used ELISA and immunocytochemistry to measure changes in the IL-6 concentration and NFkappaB translocation induced by the Ca(2+) chelator EGTA, the broad-spectrum Ca(2+) channel inhibitor ruthenium red, and the TRPV1 antagonist iodo-resiniferatoxin (I-RTX). They applied the Ca(2+) dye Fluo-4 AM to measure changes in intracellular Ca(2+) at elevated pressure induced by I-RTX and confirmed TRPV1 expression in microglia using PCR and immunocytochemistry. In DBA/2 retina, elevated intraocular pressure increased microglial IL-6 in the ganglion cell layer. Elevated hydrostatic pressure (24 hours) increased microglial IL-6 release, cytosolic NFkappaB, and NFkappaB translocation in vitro. These effects were reduced substantially by EGTA and ruthenium red. Antagonism of TRPV1 in microglia partially inhibited pressure-induced increases in IL-6 release and NFkappaB translocation. Brief elevated pressure (1 hour) induced a significant increase in microglial intracellular Ca(2+) that was partially attenuated by TRPV1 antagonism. Elevated pressure induces an influx of extracellular Ca(2+) in retinal microglia that precedes the activation of NFkappaB and the subsequent production and release of IL-6 and is at least partially dependent on the activation of TRPV1 and other ruthenium red-sensitive channels.

Spore germination of fungi belonging to Aspergillus species under deep-sea conditions

Wind-blown dry fungal spores and mycelial fragments from the nearest landmass or terrestrial run-off may find their way to the deep sea by hitching a ride on other sinking detrital particles. Once in the deep, they are affected by elevated hydrostatic pressure, low temperature and low nutrients. We have examined effects of these on germination of spores from a few deep-sea Aspergillus isolates. Spores from most of the fungi germinated under elevated hydrostatic pressure at 30 °C. The ambient temperature of the deep sea, ∼4–5 °C, was found to inhibit spore germination totally. Sediment extracts prepared in seawater promoted spore germination as did additions of dimethylsulfoxide and sucrose, but only at 30 °C/200 bar pressure and not at 4–5 °C. Heat shock of 15 min at 50 °C helped in breaking the dormancy of the spores and induced germination at 5 °C at 1 bar pressure but not at 200 bar. More than 90% of the spores from several deep-sea Aspergillus isolates and the terrestrial isolate of Aspergillus terreus lost viability within 16–17 days of incubation at 5 °C/1 bar. About 2–3% remained viable for more than 3 months at 5 °C/1 bar. Mycelial fragments showed growth and biomass production under elevated pressure at 5 °C. These results indicate that building biomass under deep-sea conditions from spores is not a viable option for the deep-sea Aspergillus isolates. Mycelial fragments, on the other hand, are more likely to grow.

Elevated hydrostatic pressure promotes protein recovery from formalin-fixed, paraffin-embedded tissue surrogates

High-throughput proteomic studies on formalin-fixed, paraffin-embedded (FFPE) tissues have been hampered by inefficient methods to extract proteins from archival tissue and by an incomplete knowledge of formaldehyde-induced modifications to proteins. We previously reported a method for the formation of ‘tissue surrogates' as a model to study formalin fixation, histochemical processing, and protein retrieval from FFPE tissues. In this study, we demonstrate the use of high hydrostatic pressure as a method for efficient protein recovery from FFPE tissue surrogates. Reversal of formaldehyde-induced protein adducts and crosslinks was observed when lysozyme tissue surrogates were extracted at 45 000 psi and 80–100°C in Tris buffers containing 2% sodium dodecyl sulfate and 0.2 M glycine at pH 4. These conditions also produced peptides resulting from acid-catalyzed aspartic acid cleavage. Additives such as trimethylamine N-oxide or copper (II) chloride decreased the total percentage of these aspartic acid cleavage products, while maintaining efficient reversal of intermolecular crosslinks in the FFPE tissue surrogates. Mass spectrometry analysis of the recovered lysozyme yielded 70% sequence coverage, correctly identified all formaldehyde-reactive amino acids, and demonstrated hydrolysis at all of the expected trypsin cleavage sites. This study demonstrates that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues for proteomic analysis.

Ab initiocalculations of the mechanical properties of SrAl2O4 stuffed tridymite

We report for the first time the complete set of elastic coefficients of the mechanoluminescent material SrAl2O4 stuffed tridymite determined by the first-principles plane-wave pseudopotential total energy method. We calculate other mechanical properties (i.e., bulk modulus, Young’s modulus, and Poisson’s ratio) of this material from the elastic coefficients determined, and compare them with the corresponding experimental and calculated results of typical oxides, indicating that SrAl2O4 stuffed tridymite is a relatively soft ceramic oxide. In addition, we investigate the crystal structure of SrAl2O4 stuffed tridymite at elevated hydrostatic pressures up to 10GPa and confirm anisotropic deformation in the SrAl2O4 lattice.

Tight junctions containing claudin 4 and 6 are essential for blastocyst formation in preimplantation mouse embryos

The trophectoderm (TE) is the first epithelium to be generated during mammalian early development. The TE works as a barrier that isolates the inner cell mass from the uterine environment and provides the turgidity of the blastocyst through elevated hydrostatic pressure. In this study, we investigated the role of tight junctions (TJs) in the barrier function of the TE during mouse blastocyst formation. RT-PCR and immunostaining revealed that the mouse TE expressed at least claudin 4, 6, and 7 among the 24 members of the claudin gene family, which encode structural and functional constituents of TJs. When embryos were cultured in the presence of a GST-fused C-terminal half of Clostridium perfringens enterotoxin (GST-C-CPE), a polypeptide with inhibitory activity to claudin 4 and 6, normal blastocyst formation was remarkably inhibited; the embryos had no or an immature blastocoel cavity without expansion, and blastomeres showed a rounded shape. In these embryos, claudin 4 and 6 proteins were absent from TJs and the barrier function of the TE was disrupted; however the basolateral localization of the Na +/K +-ATPase α1 subunit and aquaporin 3, which are thought to be involved in blastocyst formation, appeared normal. These results clearly demonstrate that the barrier function of TJs in the TE is required for normal blastocyst formation.

Oxidative Stress Is an Early Event in Hydrostatic Pressure–Induced Retinal Ganglion Cell Damage

To determine whether oxidative adduct formation or heme oxygenase-1 (HO-1) expression are altered in retinal ganglion cell (RGC) cultures exposed to elevated hydrostatic pressure and in a mouse model of glaucoma. Cultured RGC-5 cells were subjected to 0, 30, 60, or 100 mm Hg hydrostatic pressure for 2 hours, and the cells were harvested. Parallel experiments examined the recovery from this stress, the effect of direct 4-hydroxy-2-nonenal (HNE) treatment, and the effect of pretreatment with resveratrol or quercetin. Mice were anesthetized and intraocular pressure was increased to 30, 60, or 100 mm Hg for 1 hour; then the retinas were harvested. HNE adduct formation and HO-1 expression were assessed by immunocytochemistry and immunoblotting. Increases of HNE-protein adducts (up to 5-fold) and HO-1 expression (up to 2.5 fold) in pressure-treated RGC-5 cells were dose dependent. During recovery experiments, HNE-protein adducts continued to increase for up to 10 hours; in contrast, HO-1 expression decreased immediately. HNE, at a concentration as low as 5 muM, led to neurotoxicity in RGC-5 cells. HNE adducts and HO-1 expression increased in the mouse retina and optic nerve after acute IOP elevation up to 5.5-fold and 2-fold, respectively. Antioxidant treatment reduced the oxidative stress level in pressure-treated RGC-5 cells. This study demonstrates that oxidative stress is an early event in hydrostatic pressure/IOP-induced neuronal damage. These findings support the view that oxidative damage contributes early to glaucomatous optic neuropathy.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores

Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.