Periods Of Hypoxia Research Articles

Oral Kohki Tea and its protective effect against in vitro ischemic damage to the bladder.

Results of several studies indicate that ischemia/reperfusion (I/R) is an etiological factor in the contractile dysfunctions induced by partial bladder outlet obstruction in animal models. In support of this hypothesis, pretreatment of rabbits with Kohki Tea (Engelhardtia chrysolepis), a Japanese herbal drink very high in antioxidant activity, significantly reduced the contractile dysfunctions induced by partial outlet obstruction. The current study was designed to determine if pretreating rabbits with Kohki Tea could protect the bladder against the contractile damage induced by in vitro ischemia followed by re-oxygenation. Forty-eight New Zealand White rabbits were separated into two groups of 24; Group 1 was pretreated by oral gavage for 3 weeks with Kohki Tea and Group 2 received vehicle (water). Each rabbit was anesthetized with pentobarbital. The urinary bladder was rapidly removed and eight longitudinal muscle strips were cut from the bladder body. Each strip was mounted in a separate 15-ml bath containing Tyrode's solution with glucose (1 mg/ml) and maintained at 37 degrees C. All strips were equilibrated for 30 min with a gas mixture of 95% O2 and 5% CO2. At the end of this period of time, all strips were stimulated with field stimulation (FS) carbachol and KCl. After the last wash, the aeration was changed to hypoxic mixture (nitrogen-CO2) without glucose. At the end of 2 hr, the aeration was changed back to the normal 95% O2 and 5% CO2, and glucose was added to the buffer. After 1 hr of re-oxygenation, a second set of stimulations was performed. In order to represent hyperreflexia, the strips were stimulated at 32-Hz FS at 5-min intervals during the hypoxic period in half of the in vitro experiments. The results showed that Kohki Tea pretreatment protected the bladder's response to FS from the detrimental effects of repetitive stimulation and the detrimental effects of both in vitro ischemia and repetitive stimulation on the contractile responses to carbachol and KCl. These data are consistent with the concept that Kohki Tea acts by protecting the bladder from cellular damage caused by hypoxia and the generation of free radicals.

Effect of graded hypoxia on activin A, prostaglandin E2 and cortisol levels in the late-pregnant sheep

The aim of the present study was to determine whether activin A concentrations are dependent on feto-placental oxygen availability and to investigate the temporal relationship of activin A with prostaglandin (PG) E(2) and cortisol. Nine fetal sheep (six hypoxic and three control) were instrumented and catheterised at 0.8 gestation. Reduced uterine blood flow was used to achieve three levels of hypoxia (mild = fetal SaO(2) 40-50%; moderate = fetal SaO(2) 30-40%; severe = fetal SaO(2) 20-30%), for 4 h on 3 consecutive days. Activin A, PGE(2) and cortisol levels were determined in maternal and fetal blood and amniotic fluid. Moderate and severe hypoxia produced a significant (P < 0.05) increase in fetal plasma activin A concentrations. The amniotic fluid activin A concentrations were 15-fold higher than those in the fetal circulation, but were unchanged by hypoxia. The fetal PGE(2) response reflected the degree of hypoxia over the 3 days, with moderate and severe hypoxia producing a significant (P < 0.05) increase in PGE(2) concentrations. Fetal plasma cortisol concentrations were increased ( P < 0.05) during all levels of hypoxia. Fetal arterial activin A was increased in response to moderate and severe hypoxia, but levels were not maintained over the hypoxic period. The increases in activin A and cortisol concentrations preceded the increase in PGE(2).

Resistance of photoreceptors in the C57BL/6-c2J, C57BL/6J, and BALB/cJ mouse strains to oxygen stress: Evidence of an oxygen phenotype

Purpose. To assess the vulnerability of retinal photoreceptors in the BALB/cJ, C57BL/6J, and C57BL/6-c2J (c2J) mouse strains to hypoxic and hyperoxic stress.Methods. Mice were raised in dim cyclic light. Pups aged postnatal day 7 (P7) were exposed to hypoxia (11–12% oxygen) for periods up to 23 days. Adult mice were exposed to either hypoxia (12% oxygen) or to hyperoxia (75% oxygen) for up to 2 weeks. Using the TUNEL (terminal dUTP-mediated nick end labeling) technique retinas were examined for cell death.Results. In juvenile mice, hypoxia induced a robust increase in photoreceptor death in the C57BL/6J strain and a weaker increase in the C57BL/6-c2J strains. In the adult, hypoxia was associated with a small reduction in photoreceptor death in the C57BL/6-c2J strains. Hyperoxia caused substantial photoreceptor death in both the C57BL/6-c2J and C57BL/6J strains. The BALB/cJ strain was more resistant to oxygen stress than the C57BL strains.Conclusions. The difference in oxygen vulnerability between C57BL/6J and BALB/c strains may provide a useful starting point for the analysis of genetic regulation of this vulnerability. The resistance of the C57BL/6-c2J substrains to hypoxia may reflect their degenerative status.

Hypoxia increases Hsp90 binding to eNOS via PI3K-Akt in porcine coronary artery endothelium

This study examines the molecular mechanisms by which hypoxia regulates phosphorylated endothelial nitric oxide synthase (eNOS) activity and NO production in porcine coronary artery endothelial cells (PCAEC). Exposure to hypoxia (pO2=10 mmHg) for periods up to 3 h resulted in a time-dependent increase in eNOS protein expression and an early (15 min) and sustained increase in eNOS phosphorylation at Ser-1177. Exposure to hypoxia for 30 min led to a doubling in eNOS activity (control=6.2±4.4 vs hypoxia=14.1±5.0 fmol cGMP/μg protein, P<0.05) and NO release (control=5.9±0.8 vs hypoxia=11.8±1.2 nM/μg protein, P<0.05). Hypoxia also led to a significant increase in Akt phosphorylation and upregulation of Hsp90 binding to eNOS. Pretreatment of cells with either 1 μg/ml geldanamycin (a specific inhibitor of Hsp90) or 500 nM wortmannin (a specific PI3 kinase inhibitor) suppressed hypoxia-stimulated Akt and eNOS phosphorylation and significantly attenuated hypoxia-stimulated Hsp90 binding to eNOS. Both eNOS activity and NO production were inhibited by geldanamycin and wortmannin. Although hypoxia led to early activation of p42/44 mitogen-activated protein kinases (MAPK), inhibition of their pathway by PD98059 did not suppress hypoxia-stimulated eNOS phosphorylation and eNOS activity. These data demonstrate that hypoxia leads to increased eNOS phosphorylation via stimulated Hsp90 binding to eNOS and activation of the PI3–Akt pathway. We conclude that a coordinated interaction between Hsp90 and PI3–Akt may be an important mechanism by which eNOS activity and NO production is upregulated in hypoxic heart.

Oxygen concentration regulates alternative oxidase expression in barley roots during hypoxia and post‐hypoxia

During flooding, when roots are submerged in oxygen‐free water, root tissue becomes hypoxic and its metabolism is characterized by fermentation processes and limited respiratory activity. After returning to aerobic conditions (post‐hypoxic period) high respiration rates together with symptoms of oxidative stress are observed. Plant mitochondria have two terminal oxidases: a cytochrome oxidase with high affinity to oxygen and an alternative (cyanide resistant) oxidase (AOX) with a relatively low oxygen affinity. We compared mitochondrial respiration and AOX expression immediately after hypoxic and during post‐hypoxic period. Four‐day‐old barley (Hordeum vulgare L. cv Gregor) seedlings were transferred for 5 days to Knop nutrient medium flushed with air (control) or nitrogen (hypoxia) and after returned for 24 h to aerated nutrient medium (post‐hypoxia). NADH/NAD+ + NADH and UQH2/UQtotal ratios increased in hypoxia‐treated roots. After the hypoxic roots were returned to aerated medium, increases in respiration rate and ATP concentration were observed. Mitochondria isolated from barley roots at the end of hypoxic period exhibited high respiratory rates as compared to mitochondria from control and post‐hypoxic roots. Control root mitochondria expressed high AOX capacity in the presence of pyruvate and DTT. Mitochondria isolated at the end of the hypoxic period were highly cyanide sensitive under AOX‐activating conditions, however, after 24 h of post‐hypoxia, AOX capacity was comparable to that observed in the control. The capacity of AOX was correlated with the amount of AOX protein determined by Western blotting. Faint or no bands were observed immediately after hypoxia with the AOX protein appearing again during the post‐hypoxic period. Examination of AOX transcript levels showed no significant differences between control, hypoxic and post‐hypoxic roots indicating that the regulation of AOX expression by oxygen availability in barley roots may take place at the translation level.

Hypoxia Inhibits Expression of Prolactin and Secretion of Cathepsin-D by the GH4C1 Pituitary Adenoma Cell Line

Diminished oxygen concentration within growing tumors may stimulate neovascularization by inducing both up-regulation of angiogenic factors and down-regulation of antiangiogenic agents. A potentially important molecule in the growth of pituitary adenomas is prolactin (PRL), which can be cleaved by cathepsin-D to yield a 16-kDa form (16K-PRL) with potent antiangiogenic effects. We examined the expression of PRL in cultured GH4C1 pituitary adenoma cells after exposure to hypoxia (0.1% oxygen) for periods of 12 to 36 hours. In contrast to increased expression of the angiogenic factor vascular endothelial growth factor in hypoxic cells, PRL mRNA and levels of intracellular and secreted PRL were significantly reduced under hypoxia. The reduction was not attributable to a general suppression of either transcription or protein synthesis. Although 16K-PRL was not evident in conditioned medium at physiologic pH, lowering the pH to mimic the acidic tumor microenvironment resulted in generation of 16K-PRL, which was sharply reduced in medium drawn from hypoxic cells. Production of 16K-PRL was blocked by the cathepsin-D inhibitor pepstatin-A, and the reduced 16K-PRL formation in hypoxic-conditioned medium correlated with a decrease in secretion of cathepsin-D and its precursor, procathepsin-D. Thus, hypoxia acts upon GH4C1 cells to increase vascular endothelial growth factor expression, decrease PRL synthesis, and suppress conversion of PRL to 16K-PRL via inhibition of cathepsin-D proteolysis. These mechanisms may act in concert to stimulate angiogenesis in prolactinomas.

Inhibiting caspase-8 after injury reduces hypoxic–ischemic brain injury in the newborn rat

A broad spectrum caspase inhibitor reduces brain injury. Will a caspase-8 inhibitor provide protection? Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-8 activity in the right cortex was measured enzymatically. Caspase-8 activity was increased at 12 and 24 h after injury and IETD-CHO, (Ac-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Pro-Ile-Glu-Thr-Asp-CHO, CHO is aldehyde) a cell permeable caspase-8 inhibitor, given by i.c.v. injection after the hypoxic period eliminated this increase with significant effect at 15 and 50 μg/pup (1.7 μmol/kg). Thirty pups were randomly assigned to receive 50 μg/pup of IETD-CHO or vehicle i.c.v. immediately after the hypoxic period. The loss of brain weight in the right hemisphere 22 days after injury was 29±5% in the vehicle-treated animals and 12±5% in the IETD-CHO-treated animals ( P<0.05). Inhibiting caspase-8 activity after hypoxic–ischemic brain injury reduces brain injury.

Benthic foraminifers from the continental shelf and slope of the Gulf of Mexico: an indicator of shelf hypoxia

Benthic foraminifers from 74 core-top sediment samples collected primarily from the continental shelf of the Gulf of Mexico were analyzed to determine a microfaunal indicator for shelf hypoxia to be used in future paleoenvironmental studies. Principal component analysis (PCA) and cluster analysis (CA) of 93 species recognized factors/clusters that were similar to previous investigations of the benthic foraminifers, except that both analyses also identified PCA6/CA6 in the area where hypoxic conditions have been observed. Three low-oxygen-tolerant species, Pseudononion atlanticum, Epistominella vitrea, and Buliminella morgani have high factor loadings in PCA6. The cumulative percentage of three species is defined as the PEB (PEB, Pseudononion, Epistominella, Buliminella) index. The highest PEB values observed in the 74 surface sediment samples occur in the zone of recognized hypoxia on the Louisiana shelf. Values of the PEB index are also elevated along the southern Texas coastline, suggesting that this area may experience periodic hypoxia as well.

Performing at extreme altitude: muscle cellular and subcellular adaptations.

This review reports on the collaborative efforts of the Department of Physiology of the University of Geneva headed by Paolo Cerretelli, the Research Institute at the Federal School of Physical Education in Magglingen and the Department of Anatomy of the University of Bern to elucidate the functional and structural conditions for and consequences of climbing successfully at altitudes in excess of 8000 m. Using a combination of physiological whole body measurements with biochemical, histochemical and morphometric analyses of muscle biopsy samples we were able to establish specific phenotypical alterations of muscle tissue exposed to extreme hypoxia and stress for prolonged periods of time. The decline in aerobic work capacity could be shown to be a consequence of a loss of muscle mass as well as of muscle tissue oxidative capacity whereby muscle capillarity was found to be maintained. The degradation of muscle tissue was further characterized by an increase in muscle lipofuscin. The latter is believed to be the consequence of lipid peroxidation eventually related to mitochondrial loss. Current work ensuing from our long-term collaboration suggests that Sherpas might be protected against the damaging effect of hypoxia by antioxidant mechanisms protecting their muscles under the conditions of extreme altitude.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

Mechanisms of sevoflurane-induced myocardial preconditioning in isolated human right atria in vitro.

The authors examined the role of adenosine triphosphate-sensitive potassium channels and adenosine A(1) receptors in sevoflurane-induced preconditioning on isolated human myocardium. The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34 degrees C; stimulation frequency, 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation. Seven minutes before hypoxia reoxygenation, muscles were exposed to 4 min of hypoxia and 7 min of reoxygenation or 15 min of sevoflurane at concentrations of 1, 2, and 3%. In separate groups, sevoflurane 2% was administered in the presence of 10 microm HMR 1098, a sarcolemmal adenosine triphosphate-sensitive potassium channel antagonist; 800 microm 5-hydroxy-decanoate, a mitochondrial adenosine triphosphate-sensitive potassium channel antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A(1) receptor antagonist. Recovery of force at the end of the 60-min reoxygenation period was compared between groups (mean +/- SD). Hypoxic preconditioning (90 +/- 4% of baseline) and sevoflurane 1% (82 +/- 3% of baseline), 2% (92 +/- 5% of baseline), and 3% (85 +/- 7% of baseline) enhanced the recovery of force after 60 min of reoxygenation compared with the control groups (52 +/- 9% of baseline). This effect was abolished in the presence of 5-hydroxy-decanoate (55 +/- 14% of baseline) and 8-cyclopentyl-1,3-dipropylxanthine (58 +/- 16% of baseline) but was attenuated in the presence of HMR 1098 (73 +/- 10% of baseline). In vitro, sevoflurane preconditions human myocardium against hypoxia through activation of adenosine triphosphate-sensitive potassium channels and stimulation of adenosine A(1) receptors.

Effects of chronic hypoxia on inward rectifier K(+) current ( I(K1)) in ventricular myocytes of crucian carp (Carassius carassius) heart.

Some ectothermic vertebrates show unusually good tolerance to oxygen shortage and it is therefore assumed that they might, as a defense mechanism, decrease number or activity of ion channels in order to reduce membrane leakage and thereby ATP-dependent ion pumping in hypoxia. Although several studies have provided indirect evidence in favor of this 'channel arrest' hypothesis, only few experiments have examined activity of ion channels directly from animals exposed to chronic hypoxia or anoxia in vivo. Here we compare the inwardly rectifying K(+) current (I(K1)), a major leak and repolarizing K(+) pathway of the heart, in cardiac myocytes of normoxic and hypoxic crucian carp, using the whole-cell and cell-attached single-channel patch-clamp methods. Whole-cell conductance of I(K1) was 0.5 +/- 0.04 nS/pF in normoxic fish and did not change during the 4 weeks hypoxic (O2 < 0.4 mg/l; 2.68 mmHg) period, meanwhile the activity of Na(+)/K(+)ATPase decreased 33%. Single-channel conductance of the I(K1) was 20.5 +/- 0.8 pS in control fish and 21.4 +/- 1.1 pS in hypoxic fish, and the open probability of the channel was 0.80 +/- 0.03 and 0.74 +/- 0.04 ( P > 0.05) in control and hypoxic fish, respectively. Open and closed times also had identical distributions in normoxic and hypoxic animals. These results suggest that the density and activity of the inward rectifier K(+) channel is not modified by chronic hypoxia in ventricular myocytes of the crucian carp heart. It is concluded that instead of channel arrest, the hypoxic fish cardiac myocytes obtain energy savings through 'action potential arrest' due to hypoxic bradycardia.

Enhanced energy metabolism during cold hypoxic organ preservation: studies on rat liver after pyruvate supplementation

Previous studies have indicated that pyruvate is able to reduce ischaemia/reperfusion (I/R) injury in a variety of tissues, but a full understanding of the effects is lacking. In this current preliminary study, magnetic resonance spectroscopy (MRS) was used to investigate the biochemical effects of differing concentrations of pyruvate (3 and 15 mM) on liver metabolism during the cold hypoxic preservation period itself, in order to gain insight into possible mechanisms. Hepatic lactate, alanine, and succinate levels were increased in livers preserved with 15 mM pyruvate added to the University of Wisconsin (UW) solution and were generally elevated (but to a lesser degree) in livers flushed with 3 mM pyruvate, compared to those cold stored in UW alone. Further, from enzymatic assays of adenine nucleotides, 15 mM levels of pyruvate were found to maintain higher ATP levels during short periods (up to 4 h) of cold hypoxic storage than in UW stored livers, whilst energy charge ratios (after 4 and 24 h) were also higher ( P<0.01 in each case). This may arise from enhanced glycolysis secondary to an improved redox status in the pyruvate-treated livers, as evident by the increase in the levels of lactate.

Inhibiting caspase-9 after injury reduces hypoxic ischemic neuronal injury in the cortex in the newborn rat

A broad spectrum caspase inhibitor reduces hypoxic ischemic brain injury. We hypothesized that a specific caspase-9 inhibitor would provide similar protection. Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-9 activity in the right cortex was measured enzymatically. Caspase-9 activity was increased at 6, 12, and 24 h after injury. LEHD-CHO is a specific cell permeable caspase-9 inhibitor. LEHD-CHO given intracerebroventricularly (i.c.v.) into the brain after the hypoxic period eliminated the increase in caspase-9 activity. The greatest effect was at a dose of 50 μg/pup (1.6 μmol/kg). Fifty-two pups were randomly assigned to receive 50 μg/pup of i.c.v. LEHD-CHO or vehicle immediately after the hypoxic period. The loss of cortical neurons in the right hemisphere 22 days after injury was 52.0±8% in the vehicle treated animals, and 25±9% in the LEHD-CHO treated animals ( P<0.05). Inhibiting caspase-9 activity reduces loss of neurons after brain injury.

Mapacalcine specifically blocks hypoxia-induced calcium influx in rat hepatocytes.

Post ischaemic cell calcium invasion has been described as one of the main causes of graft failure. Protective effects of calcium antagonists have been investigated but are not convincing and their mechanisms of action remain unclear. In this work we tested the protective effect of a new calcium inhibitor described to block a calcium current insensitive to all known calcium blockers. Specific mapacalcine receptors were first characterized on rat hepatocytes membranes using the 125I-labeled mapacalcine. 45Ca fluxes were then measured on cultured hepatocytes submitted (or not) to an hypoxic period. The action of mapacalcine was investigated on the ischaemia-induced calcium influx. We demonstrate here that: (a) there are specific receptors for mapacalcine in rat hepatocytes; (b) Mapacalcine is able to specifically block ischaemia-induced calcium influx with an IC50 of 0.3 micro m and does not significantly interact with the basal calcium flux. Our work demonstrates that the mapacalcine receptor is a cellular structure directly involved in the phenomenon of postischaemic cell invasion by calcium. Specific block of ischaemia-induced Ca2+ influx by mapacalcine suggests that the development of a panel of pharmacological drugs acting on this receptor could lead to the discovery of therapeutic agents able to protect cells against one of the events responsible for organ failure after transplantation or simply after an ischaemic period. Moreover, identification of the cellular protein which binds mapacalcine may become an important step in the research of mechanisms involved in postischaemic cell invasion by calcium.

Resting respiratory behavior in minimally instrumented toads--effects of very long apneas on blood gases and pH.

Resting respiratory behavior of Bufo marinus in minimally instrumented toads is described for a period of 24 hours in which the animals are left undisturbed. Torpor-related long apneas are described and their implications for blood gas levels are investigated. Results show that the resting ventilation rate of Bufo marinus is much lower than that reported so far. Levels of arterial oxygen, carbon dioxide, and pH are monitored during artificial long apneas induced by anesthesia. The toads showed an unexpected ability to unload carbon dioxide by non-respiratory means, even while being kept on dry plastic box with no access to water. Oxygen arterial partial pressure dropped to very low levels after one hour of apnea. This suggests that these animals may endure very well severe hypoxia for long periods of time while in torpor.

Upregulation of NMDA receptor and neuronal NADPH-d/NOS expression in the nodose ganglion of acute hypoxic rats

Nitric oxide may serve as a neuronal messenger in the regulation of cardiorespiratory function via the N-methyl- d-aspartate (NMDA) receptor-mediated neuronal nitric oxide synthase (nNOS) activation. Since hypoxic stress would drastically influence the cardiorespiratory function, the present study aimed to examine if the expression of nNOS and NMDA receptor subunit 1 (NMDAR1) in the nodose ganglion (NG) would alter under different extents of hypoxia treatment. The nicotinamine adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, nNOS and NMDAR1 immunofluorescence were used to examine nNOS and NMDAR1 expression in the NG following exposing of adult rats in the altitude chamber (0.27 atm, P o 2 =43 torr) for 2 and 4 h. The present results showed that NADPH-d, nNOS and NMDAR1 reactivities were co-localized in the NG under normoxic and hypoxic environment. Quantitative evaluation revealed that about 43% of neurons in the NG showed positive response for NADPH-d/nNOS and NMDAR1 reactivities. However, in animals subjected to hypoxia, both the percentage and the staining intensity of NADPH-d/nNOS and NMDAR1 labeled neurons were drastically increased. The percentage of NADPH-d/nNOS and NMDAR1-immunoreactive neurons in the NG was raised to 68% as well as 77%, respectively, following 2 and 4 h of hypoxic exposure. The magnitude of up-regulation was positively correlated with the duration of hypoxic periods. No significant cell loss was observed under this experimental paradigm. These findings suggest that different extents of hypoxia might induce the higher expression of nNOS and NMDAR1 in the NG, which could contribute to the neuronal integration as responding to the different physiological demands under hypoxic stress.

Estuarine epifauna recruit despite periodic hypoxia stress

In some estuaries, the recruitment of epifaunal benthic invertebrates coincides with a significant environmental stress, low water-column dissolved oxygen, termed hypoxia (≥2 mg O2 l–1). Recruitment of epifaunal species was measured in the lower York River, a subestuary of the Chesapeake Bay, USA, which experiences predictable, periodic hypoxia associated with neap/spring tidal cycling during summer. Recruitment substrata were exposed during 48-h deployments in two areas with differing levels of hypoxia, and epifauna were allowed to recruit during periods of low oxygen (neap tides) and high oxygen (spring tides) in 1996 and 1997. Recruitment was often high during neap tides, even when severe oxygen depletion (<0.5 mg O2 l–1, <0.71 ml O2 l–1) occurred during deployments; indeed, peak recruitment episodes of several dominant epifaunal taxa, and of total epifauna, coincided with hypoxic events during both summers. Increased recruitment during neap tides suggests that factors besides hypoxia influenced recruitment in the York River; these factors may have included changes in larval availability and lower current speeds. This study illustrates how the relationship between recruitment and large-scale stresses, such as hypoxia, may be difficult to predict, since large-scale stresses are often correlated with numerous other factors. Short-term hypoxia appears to have little effect on recruitment in the field for many epifaunal species in this ecosystem, which may explain, in part, why substrata exposed for longer durations (1 month) in this system showed few effects of hypoxia on community composition or diversity. High larval tolerance of hypoxic stress may allow communities to persist even though the summer hypoxia season coincides with the recruitment of many epifaunal species. Electronic Supplementary Material is available if you access this article at http://dx.doi.org/10.1007/s00227-002-0930-6. On that page (frame on the left side), a link takes you directly to the supplementary material.

Drowning.

Recent epidemiologic data have shown that the burden of drowning is much greater than expected. Prevention and timely rescue are the most effective means of reducing the number of persons at risk. Early bystander cardiopulmonary resuscitation is the most important factor for survival after submersion. Cerebral damage is a serious threat when the hypoxic period is too long. In most situations, low body temperature is an indication of the severity of the drowning incident. Sometimes hypothermia that occurs during the submersion period can be brain protective. There is also new evidence to support the strategy of inducing mild hypothermia for a period of 12 to 24 hours in comatose drowning victims. In immersed patients, hypothermia should be treated. The most appropriate technique will depend on the available means in the hospital and the condition of the patient. Treatment of pulmonary complications depends on the lung injury that occurred during aspiration and the bacteria involved in aspiration. Understanding the pathophysiology of drowning may help us to understand lung injuries and ischemic brain injuries.

Protective actions of rat gastric epithelial E-cadherin expression against epithelial barrier dysfunctions induced by chemical hypoxia-reoxygenation in vitro.

E-cadherin expressed on gastric epithelium is reported to form adherence junctions and stabilize barrier functions. While hypoxia-reoxygenation is well known to cause gastric mucosal injury during reoxygenation, gastric E-cadherin actions against this stress remain unclear. In this study, using the oxygen depleting agent thioglycolic acid we examined whether E-cadherin expressed on rat cultured gastric epithelial cells has protective actions against epithelial barrier dysfunction induced by chemical hypoxia-reoxygenation. Chemical hypoxia was induced by incubating cells with 5 mm thioglycolic acid in glucose free medium for 60 min. Cells were then reoxygenated for 240 min by changing to normal medium. The expression of E-cadherin on the cell surface was measured with an enzyme immunoassay, and epithelial permeability was determined by the diffusion rate of FITC-dextran through the cell layer. E-cadherin expression increased during the 60 min hypoxic period, accompanied by activation of protein kinase C, protein kinase G and protein kinase A. The increased expression significantly diminished, but was considerably higher than the control values during reoxygenation for 180 min, which was partially due to generation of reactive oxygen species but not to activation of protein kinase. Conversely, epithelial permeability was stabilized during hypoxia, but increased only for 30 min of reoxygenation, probably due to generation of reactive oxygen species. Epithelial permeability during hypoxia was elevated by a combination of all the protein kinase inhibitors. An increase in the expression of E-cadherin during hypoxia through the activation of the kinases is likely to stabilize epithelial barrier functions. The reactive oxygen species generated during 30 min reoxygenation increased the molecular expression of E-cadherin less than during hypoxic stress. The transient break in the barrier functions caused by reactive oxygen species during reoxygenation appears to overcome the reactive oxygen species mediated cytoprotective action increasing E-cadherin expression.