Hyperoxia prevents carrageenan-induced enlargement of functional residual lung capacity in rats

Experimental pneumonia induced by intratracheal application of carrageenan or paraquat increases the functional residual lung capacity (FRC) in rats. The mechanism of this increase is not clear, but a decrease in PO(2) may be involved. To test this possibility, we attempted to eliminate the PO(2) decrease in carrageenan-treated rats by exposing them to hyperoxia. Animals of the first group were exposed to 7 days of hyperoxia (F(I)O(2) 0.78-0.84, group Car+O(2)) after intratracheal application of carrageenan (0.5 ml of 0.7 % carrageenan in saline), whereas animals of the second group were given the same dose of carrageenan but breathed air (group Car+A). The third group of rats was kept for seven days in hyperoxia (group O(2)) and the fourth group served as controls (C). The animals were then anesthetized and intubated and their ventilatory parameters and FRC were measured during air breathing. Carrageenan application induced a FRC increase (Car+A 2.0+/-0.2 ml, C 1.6+/-0.1 ml), which was not seen in carrageenan-treated rats exposed to hyperoxia (Car+O(2) 1.6+/-0.1 ml). Hyperoxia alone did not affect the value of FRC (O(2) 1.5+/-0.1 ml). These results support the hypothesis that a decrease in PO(2) plays an important role in the carrageenan-induced increase of FRC in rats.     

Regional alveolar hypoxia does not affect air embolism-induced pulmonary edema

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema resulting from venous air embolization. Anesthetized dogs had the left upper lobe removed and a double-lumen tube placed so that right lung and left lower lobe (LLL) could be ventilated independently. Air was infused into the femoral vein for 1 h during bilateral ventilation at an inspiratory O2 fraction (FIO2) of 1.0. After cessation of air infusion the LLL was then ventilated with a hypoxic gas mixture (FIO2 = 0.05) in six animals and an FIO2 of 1.0 in six other animals. Lung hydroxyproline content was measured as an index of lung dry weight. LLL bloodless lobar wet weight-to-hydroxyproline ratio was 0.33 +/- 0.06 mg/micrograms in the animals exposed to LLL hypoxia and 0.37 +/- 0.03 mg/micrograms (NS) in the animals that had a LLL FIO2 of 1. Both values were significantly higher than our laboratory normal values of 0.19 +/- 0.01 mg/micrograms. We subsequently found in four more dogs exposed to global alveolar hypoxia before and after air embolism that the air injury itself significantly depressed the hypoxic vasoconstrictor response. We conclude that regional alveolar hypoxia has no effect on pulmonary edema formation due to air embolism. The most likely reason for these findings is that the air embolism injury itself interfered with hypoxic pulmonary vasoconstriction.     

Arterial hypoxia does not affect subchondral pressure and regional blood flow

The influence of arterial hypoxia on bone marrow pressure, regional blood flow and oxygen and carbon dioxide tensions was investigated by simultaneous and continuous measurements in the femoral condyles of 8 rabbits. Arterial hypoxia was obtained by hypoventilation. The subchondral gas tensions and regional blood flow were measured by a previously described technique based on mass spectrometry. Arterial hypoxia caused a significant decrease in subchondral oxygen tension and an increase in subchondral carbon dioxide tension. There was no significant change in bone marrow pressure and regional blood flow.     

Naloxone does not affect ventillatory responses to hypoxia and hypercapnia in rats

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) or naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.     

DNA demethylation induced by 5-azacytidine does not affect fragile X expression.

Experiments were performed to determine the role of DNA demethylation in fragile X expression. Fragile X positive lymphoblastoid cells were treated with 5-azacytidine and harvested for analysis of fragile X expression both directly following treatment and after a recovery period in the absence of the drug. The effectiveness of 5-azacytidine treatment in inducing DNA demethylation was concurrently monitored by analysis of methylation changes at random autosomal loci in isolated DNA from treated cells. Under conditions where 5-azacytidine was found to inhibit fragile X expression, no DNA demethylation was observed. At the time when demethylation did occur, fragile X expression was not affected. These results strongly indicate that DNA demethylation is not involved in fragile X expression.     

Hypercapnia protects erythrocytes against free radical damage induced by hypoxia in exposed rats

Several studies report that hypoxic exposure induces free radical oxidative damage in various tissues. The mechanism of this damage includes membrane lipid peroxidation which can be easily detected by measuring fluorescent end-products of the process, i.e. lipofuscin-like pigments. Four day exposure of rats to hypoxia (10% O(2)) increased the level of lipofuscin-like pigments in erythrocytes up to 9 fold. This increase was completely prevented when the animals were exposed to hypercapnia (4.3% CO(2)) in addition to hypoxia. We studied the possible mechanism of the hypercapnic protection on isolated erythrocyte membranes in vitro. Lipid peroxidation was initiated by incubation of the membranes with iron ions and ascorbate. Production of malonaldehyde, the precursor of lipofuscin-like pigments, was strongly inhibited in bicarbonate buffer. Similarly the production of lipofuscin-like products was damped. These experiments suggest that the protective effect of hypercapnia might consist in direct interaction of CO(2) with free radical processes.     

Charring does not affect wood infestation by subterranean termites

Fire is an important part of forest ecosystems, as is the insect fauna. Changes in wood brought about by fire may alter the ability of termites to use the wood, interrupting the decay cycle of woody debris. The ability of termites to find, infest, and feed upon wood after it had been charred was evaluated in the laboratory and field. Eastern subterranean termites, Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae), fed on char from burned wood had significantly reduced numbers of protozoa compared to termites fed on pine shavings, but significantly more than starved termites. The ability of termites to find and infest wood was not affected by surface charring. In a laboratory choice test, there were no significant differences in the onset of feeding by termites between charred and non‐charred wood boards. Likewise in the field, no differences were observed in the time to initial attack by termites on charred and non‐charred wood boards or bolts. Because termites will likely survive fires of low to moderate intensity, in most cases, there should be no disruption of the termite contribution to forest nutrient and carbon cycles.     

Dietary polyunsaturated fatty acids alter myocardial protein kinase C expression and affect cardioprotection induced by chronic hypoxia

We examined the influence of dietary fatty acid (FA) classes on the expression of protein kinase C (PKC) delta and epsilon in relation to the cardioprotective effects of chronic intermittent hypoxia (CIH). Adult male Wistar rats were fed a nonfat diet enriched with 10% lard (saturated FA [SFA]), fish oil (n-3 polyunsaturated FA [n-3 PUFA]), or corn oil (n-6 PUFA) for 10 weeks. After 4 weeks on the diet, each group was divided into two subgroups that were either exposed to CIH in a barochamber (7000 m, 8 hrs/ day) or kept at normoxia for an additional 5-6 weeks. A FA phospholipid profile and Western blot analysis of PKC were performed in left ventricles. Infarct size was assessed in anesthetized animals subjected to 20-min coronary artery occlusion and 3-hr reperfusion. CIH decreased the n-6/n-3 PUFA ratio in all groups by 23% independently of the initial value set by various diets. The combination of n-3 diet and CIH had a stronger antiarrhythmic effect during reperfusion than the n-3 diet alone; this effect was less pronounced in rats fed the n-6 diet. The normoxic n-6 group exhibited smaller infarctions (by 22%) than the n-3 group. CIH decreased the infarct size in n-3 and SFA groups (by 20% and 23%, respectively) but not in the n-6 group. Unlike PKC epsilon, the abundance of PKC delta in the myocardial particulate fraction was increased by CIH except for the n-6 group. Myocardial infarct size was negatively correlated (r=- 0.79) with the abundance of PKC delta in the particulate fraction. We conclude that lipid diets modify the infarct size-limiting effect of CIH by a mechanism that involves the PKC delta-dependent pathway.     

Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans.

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-alpha-tocopherol (800 mg/day for 3 wk) and alpha-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum alpha-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po(2) declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.     

Lack of the nociceptin receptor does not affect acute or chronic nociception in mice

The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor ORL-1, also designated opioid receptor 4 (OP(4)) are involved in the modulation of nociception. Using OP(4)-knockout mice, we have studied their response following opioid receptor stimulation and under neuropathic conditions.In vas deferens from wild-type and OP(4)-knockout mice, DAMGO (mu/OP(3) agonist), deltorphine II (delta/OP(1) agonist) and (-)-U-50488 (kappa/OP(2) agonist) induced similar concentration-dependent inhibition of electrically-evoked contractions. Naloxone and naltrindole (delta/OP(1) antagonists) shifted the curves of DAMGO (pA(2)=8.6) and deltorphine II (pA(2)=10.2) to the right, in each group. In the hot-plate assay, N/OFQ (10 nmol per mouse, i.t.) increased baseline latencies two-fold in wild-type mice while morphine (10mg/kg, s.c.), deltorphine II (10 nmol per mouse, i.c.v.) and dynorphin A (20 nmol per mouse, i.c.v.) increased hot-plate latencies by about four- to five-fold with no difference observed between wild-type and knockout mice. Furthermore, no change was evident in the development of the neuropathic condition due to chronic constriction injury (CCI) of the sciatic nerve, after both thermal and mechanical stimulation.Altogether these results suggest that the presence of OP(4) receptor is not crucial for (1) the development of either acute or neuropathic nociceptive responses, and for (2) the regulation of full receptor-mediated responses to opioid agonists, even though compensatory mechanisms could not be excluded.     

Arrival order among native plant functional groups does not affect invasibility of constructed dune communities

Different arrival order scenarios of native functional groups to a site may influence both resource use during development and final community structure. Arrival order may then indirectly influence community resistance to invasion. We present a mesocosm experiment of constructed coastal dune communities that monitored biotic and abiotic responses to different arrival orders of native functional groups. Constructed communities were compared with unplanted mesocosms. We then simulated a single invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata), a dominant exotic shrub of coastal communities. We evaluated the hypothesis that plantings with simultaneous representation of grass, herb and shrub functional groups at the beginning of the experiment would more completely sequester resources and limit invasion than staggered plantings. Staggered plantings in turn would offer greater resource use and invasion resistance than unplanted mesocosms. Contrary to our expectations, there were few effects of arrival order on abiotic variables for the duration of the experiment and arrival order was unimportant in final community invasibility. All planted mesocosms supported significantly more invader germinants and significantly less invader abundance than unplanted mesocosms. Native functional group plantings may have a nurse effect during the invader germination and establishment phase and a competitive function during the invader juvenile and adult phase. Arrival order per se did not affect resource use and community invasibility in our mesocosm experiment. While grass, herb and shrub functional group plantings will not prevent invasion success in restored communities, they may limit final invader biomass.     

Hibernation does not affect memory retention in bats

Long-term memory can be critically important for animals in a variety of contexts, and yet the extreme reduction in body temperature in hibernating animals alters neurochemistry and may therefore impair brain function. Behavioural studies on memory impairment associated with hibernation have been almost exclusively conducted on ground squirrels (Rodentia) and provide conflicting results, including clear evidence for memory loss. Here, we for the first time tested memory retention after hibernation for a vertebrate outside rodents—bats (Chiroptera). In the light of the high mobility, ecology and long life of bats, we hypothesized that maintenance of consolidated memory through hibernation is under strong natural selection. We trained bats to find food in one out of three maze arms. After training, the pre-hibernation performance of all individuals was at 100 per cent correct decisions. After this pre-test, one group of bats was kept, with two interruptions, at 7°C for two months, while the other group was kept under conditions that prevented them from going into hibernation. The hibernated bats performed at the same high level as before hibernation and as the non-hibernated controls. Our data suggest that bats benefit from an as yet unknown neuroprotective mechanism to prevent memory loss in the cold brain.     

Prostacyclin does not affect insulin secretion in humans

The effects of Prostacyclin (PGI₂) infusion on insulin secretion and glucose tolerance were investigated in 7 healthy subjects. PGI₂ infusion caused no statistically significant changes of either glucose or insulin concentration, over the range 2.5–20 ng/Kg/min. A constant PGI₂ infusion (10 ng/Kg/min) did not inhibit acute insulin responses to a glucose (20 g i.v.) pulse (response before PGI₂ = 612±307%; during PGI₂ = 515±468%, mean ± SD, mean change 3–5 min insulin, % basal; P=NS). Glucose disappearance rates were similar after the first and second glucose pulse.Thus, in contrast to PGE₂, PGI₂ does not affect insulin secretion nor glucose disposal at doses producing platelet and vascular changes. It is hypothesized that an altered PGI₂/PGE₂ balance in diabetes may represent a link between vascular, platelet and metabolic changes.