Ovine placenta at high altitudes: comparison of animals with different times of adaptation to hypoxic environment

Fetal growth and newborn weight from ovine gestations at high altitudes (HA) are greater in ewes that live at HA for several generations than in those native to low altitudes (LA) exposed to HA only during pregnancy. Because the placenta is a key regulator of fetal growth, the present study compared placental characteristics in term pregnancies among ewes native to HA and LA. Conception occurred at HA and ewes continued to reside at HA throughout pregnancy or conception occurred at LA and ewes were transported to HA or remained at LA (controls). Ewes native to LA were moved to HA shortly after mating (group LH) and joined with pregnant ewes native to HA (group HH). After parturition, placental cotyledons were counted and measured for total area and histological estimation of surface occupied by vasculature. The total surface of the cotyledons and surface occupied by vasculature were greater at HA, whereas the number of cotyledons was smaller at HA. These changes were more pronounced in ewes of the HH compared with the LH group. The present study showed that exposure to HA induces, in pregnant ewes, placental morphological changes that may improve maternal-fetal exchange. Moreover, because of accentuation of placental changes in ewes with long-term residence at HA, this appears to be an efficient mechanism of adaptation to hypobaric hypoxia.     

Effect of calcium concentration on textural properties of high and low acyl mixed gellan gels

Textural properties of 1% low and high acyl gellan gels and their mixtures were studied using compression tests and the microcentrifuge-microfiltration based water holding capacity (WHC) method. Low acyl (1% LA), high acyl (1% HA) gels and mixtures of 1% 25/75 LA/HA, 50/50 LA/HA, 75/25 LA/HA gels with calcium concentrations ranging from 2 to 80 mM were studied. HA or mixed gels with a lower LA/HA ratio had a greater WHC and failure strain than that of LA or mixed gels with a higher LA/HA ratio. Gellan gels with a higher LA/HA ratio had a larger initial Young's modulus. Our study also indicates that a higher LA/HA ratio does not necessarily result in a gel with a larger failure stress, although LA gels are generally firmer than HA gels. Gel strength and WHC of HA and LA/HA mixtures may reflect both stabilization and destabilization effects of glycerate groups positioned at one of the glucose residues in each repeating tetrasaccharide unit of HA gels.     

Differential metabolic capacity of mice selected for magnitude of swim stress-induced analgesia.

Maximum oxygen consumption (Vo(2)) elicited by swimming in 20 degrees C water or by exposure to -2.5 degrees C in helium-oxygen (Helox) atmosphere is higher in mice selected for low (LA) than for high (HA) stress-induced analgesia (SIA) produced by swimming. However, this line difference is greater with respect to swim- than to cold-elicited Vo(2). To study the relationship between the analgesic and thermogenic mechanisms, we acclimated HA and LA mice to 5 degrees C or to daily swimming at 20 or 32 degrees C. Next, the acclimated mice were exposed to a Helox test at -2.5 degrees C and to a swim test at 20 degrees C to compare Vo(2) and hypothermia (DeltaT). Cold acclimation raised Vo(2) and decreased DeltaT. These effects were similar in both lines in the Helox test but were smaller in the HA than in the LA line in the swim test. HA and LA mice acclimated to 20 or 32 degrees C swims increased Vo(2) and decreased DeltaT elicited by swimming, but only HA mice acclimated to 20 degrees C swims increased Vo(2) and decreased DeltaT in the Helox test. We conclude that the between-line difference in swim Vo(2) results from a stronger modulation of thermogenic capacities of HA mice by a swim stress-related mechanism, resulting in SIA. We suggest that the predisposition to SIA observed in laboratory as well as wild animals may significantly affect both the results of laboratory measurements of Vo(2) and the interpretation of its intra- and interspecific variation.     

Heart rate variability in women exposed to very cold air (−110 °C) during whole-body cryotherapy

Heart rate monitoring was used to measure heart rate variability (HRV) at thermoneutral conditions (Ta 24 °C) in healthy women resting in supine position before and after acute and after repeated (3 times a week during a 3-month period) whole-body cryotherapies (WBC), at −110 °C. The observed acute cooling-related increase in high frequency power (HFP) of RR-intervals indicates an increase in cardiac parasympathetic modulation. After 3 months of repeated WBC the increase in parasympathetic tone was attenuated, which may be interpreted as an adaptation of autonomic function. The repeated WBC exposures-related increase in resting low frequency power (LFP) of RR-intervals during the 3 months resembles the response observed related to exercise training.     

Modifications of serotonergic and adrenergic receptor concentrations in the brain of aggressive Canis familiaris

The aim of the study was to measure beta-adrenergic (beta-AR) and serotonergic (5-HTR) receptor concentrations in different brain areas (frontal cortex, hippocampus, hypothalamus and thalamus) of normal and aggressive dogs. Eight adult male dogs, 4.2+/-0.6 years old, showing no clinical signs but aggression, were used for the study. Eight healthy male dogs, 4.4+/-0.8 years old, with no history of neurological and/or behavioural disorders and accidental death, were used as controls. The whole frontal cortex, hippocampus, thalamus and hypothalamus were collected after euthanasia and plasma membrane fractions obtained by ultracentrifugation. beta-AR and 5-HTR were measured by binding assays using specific radioligand [(-)[3H]CGP 12177 and 5-hydroxy[3H]-tryptamine trifluoroacetate, respectively]. A significant decrease in beta-AR levels was observed in the frontal cortex (P=0.001), hippocampus (P<0.0001), and thalamus (P<0.0001) of aggressive dogs compared to controls. As far as 5-HTR are concerned, two receptor subtypes were detected. The two subtypes were classified as low-affinity (5-HTR LA) and high-affinity (5-HTR HA) serotonergic receptors for [3H]-hydroxytryptamine, on the basis of their affinity for [3H]-hydroxytryptamine. 5-HTR LA significantly increased in the whole central nervous system (CNS) area of aggressive dogs (frontal cortex P=0.071; hippocampus P=0.0013; thalamus P<0.0001; hypothalamus P=0.0004); 5-HTR HA significantly increased only in the thalamus (P=0.0005) and hypothalamus (P=0.0002). Results suggest the possible role played by the catecholaminergic and serotonergic systems in canine aggressive behaviour. The understanding of the biological basis of canine aggression may enable the development of pharmacological treatments that would target specific neurotransmitter systems.     

Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

Anaerobic metabolism during pubertal development at high altitude

In a previous study we showed that there were no differences in anaerobic metabolism between groups of 11-yr-old children living at high (3,700 m) and low (330 m) altitudes. The aim of this study is to investigate changes in this metabolism during pubertal development. We compare blood lactate concentration ([L]) after maximal bicycle exercise in 20 boys acclimatized to high altitude (HA, 12 yr old) and at low altitude in 14 boys (LA1, 12 yr old) and in 13 boys (LA2, 14 yr old). The subjects had the same level of physical fitness and the same nutritional and socioeconomic status. Pubertal development was identified by salivary testosterone concentration ([T]). Results (means +/- SE) showed 1) at the age of 12 years, [L] and [T] in HA were significantly higher than in LA1 ([L] was 9.2 +/- 0.5 vs. 6.8 +/- 0.5 mmol/l, [T] was 233 +/- 66 vs. 132 +/- 30 pmol/l), 2) [L] and [T] in HA were statistically the same as in LA2, and 3) a linear relationship between [L] and [T] was significant (P less than 0.05) in all HA and LA subjects. This suggests that the higher [L] in 12-yr-old boys living at HA could result in an enhanced anaerobic metabolism linked to an earlier gonadal maturation evaluated by testosterone level.     

Vagal Withdrawal and Susceptibility to Cardiac Arrhythmias in Rats with High Trait Aggressiveness

Personality characteristics, e.g. aggressiveness, have long been associated with an increased risk of cardiac disease. However, the underlying mechanisms remain unclear. In this study we used a rodent model for characterizing cardiac autonomic modulation in rats that differ widely in their level of aggressive behavior. To reach this goal, high-aggressive (HA, n = 10) and non-aggressive (NA, n = 10) rats were selected from a population (n = 121) of adult male Wild-type Groningen rats on the basis of their latency time to attack (ALT, s) a male intruder in a resident-intruder test lasting 600 s. In order to obtain information on their cardiac autonomic modulation, ECG recordings were subsequently obtained via radiotelemetry at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HA rats (ALT<90 s) displayed reduced heart rate variability, mostly in terms of lower vagal modulation compared to NA rats (ALT>600 s). Exposure to stressful stimuli (i.e. restraint and psychosocial stress) provoked similar tachycardic responses between the two groups. However, under stress conditions HA rats displayed a reduced vagal antagonism and an increased incidence of tachyarrhythmias compared to NA rats. In addition, beta-adrenergic pharmacological stimulation induced a much larger incidence of ventricular tachyarrhythmias in HA rats compared to NA counterparts. These findings are consistent with the view that high levels of aggressive behavior in rats are associated to signs of cardiac autonomic impairment and increased arrhythmogenic susceptibility that may predict vulnerability to cardiac morbidity and mortality.     

Psychopharmacologic facilitation of psychosocial therapy of violence and hyperkinesis

Experiments on naturally occurring hyperkinetic and violent dogs and cats demonstrated the usefulness of low dosages of amphetamine (0,2-1,0 mg/kg per os) in inhibiting these nonadaptive forms of behavior, permitting the development of discriminated Pavlovian and operant conditional responses. When amphetamine therapy was combined systematically with conditioning experiments and psychosocial therapy, for long enough periods of time (many weeks), the beneficial effects of this drug persisted in the nodrug state, i.e. the learning was not state-dependent. Amphetamine also ameliorated significantly conditional emotional visceral responses in dogs with low adaptation to psychologically stressful situations. The same low dosage of amphetamine which improved the behavior and learning of hyperkinetic and violent dogs disrupted the behavior and produced disorientation in normal dogs with previously stable conditional responses.     

IgG and IgM responses in high and low antibody-selected lines of chickens

Kinetics of IgG and IgM as measured by 2-mercaptoethanol-resistant (MER) and susceptible (MES) antibodies to sheep erythrocytes, respectively, were determined as correlated responses in lines of chickens selected for high (HA) and low (LA) antibody response to sheep erythrocytes. Primary response patterns for total, MER, and MES antibody differed according to the genetic line. Total antibody increased rapidly, peaked, and persisted at moderate levels in line HA, whereas both peak and persistency were lower in line LA. Levels of MES peaked and then declined in line HA chickens but persisted at low levels throughout in line LA. Titers of MER antibody were considerably greater in line HA than in line LA both on an absolute basis and as a proportion of total antibody titer. Secondary total titers were greater at five days after injection than at three days and greater for line HA than for line LA chicks. The pattern observed for MER and MES in line LA was similar to that for total antibody, as was MER in line HA. For MES the pattern was reversed in line HA.     

Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin

A switch in specificity of avian influenza A viruses' hemagglutinin (HA) from avian-like (alpha2-3 sialylated glycans) to human-like (alpha2-6 sialylated glycans) receptors is believed to be associated with their adaptation to infect humans. We show that a characteristic structural topology--and not the alpha2-6 linkage itself--enables specific binding of HA to alpha2-6 sialylated glycans and that recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans. An integrated biochemical, analytical and data mining approach demonstrates that HAs from the human-adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long alpha2-6 sialylated glycans with this topology. This could explain why H5N1 viruses have not yet gained a foothold in the human population. Our findings will enable the development of additional strategies for effective surveillance and potential therapeutic interventions for H5N1 and possibly other influenza A viruses.     

Force-velocity and 30-s Wingate tests in boys at high and low altitudes

The effects of high altitude (HA, 3,700 m) on performance during a force-velocity test (maximal anaerobic power, MAnP) and a 30-s Wingate test (mean power, P) were studied in boys 7-15 yr of age. Forty-seven children acclimatized to HA were compared with 101 living at low altitude (LA, 330 m). They had the same good nutritional status and the same level of physical activities [average 5.4 +/- 1.1 (SD) and 5.2 +/- 1.9 h/wk at HA and LA, respectively]. They performed the two tests using the same calibrated cycle ergometer. For the Wingate test, O2 uptake (VO2) during the 30 s and the peak of blood lactate concentration ([L]p) during the recovery were also measured. No difference in MAnP was observed between HA and LA. P, [L]p, and VO2 were lower at HA. This suggests that the altitude of 3,700 m did not affect the performance of the force-velocity test but reduced that of the Wingate test. This decrease in P was linked to a lower participation of glycolysis and aerobic metabolism. The latter is related to a reduced aerobic performance at HA. In addition, the slopes of the relationships between age and MAnP, P, and [L]p were the same at HA and LA, indicating that chronic hypoxia did not alter the development of the anaerobic metabolism during puberty.     

<Emphasis Type="Italic">Pinus nigra</Emphasis> Arn. ssp <Emphasis Type="Italic">salzmannii</Emphasis> early recruitment and initial seedling growth in warmer and drier locations: the role of seed and soil provenance

Current decreasing precipitation and increasing temperatures promote the likelihood of extreme drought events and may alter the recruitment capacities of tree species. Spanish black pine (Pinus nigra ssp. salzmannii) initial recruitment is being one of the most affected pine species by changing conditions with alterations in the future species distribution. In this context, a cross-exchange experiment was implemented using an outdoor nursery located in a warmer and drier location for testing different Spanish Black pine seeds and soil provenance combinations in relation to early recruitment and initial seedling growth. Soil and seeds were collected at a high (HA, 1641 m.a.s.l.) and low (LA, 1099 m.a.s.l.) altitude in Cuenca Mountains (Spain). Then, a cross-sown experiment using HA and LA soils and seeds was set up in an outdoor nursery, which is located in Albacete (704 m.a.s.l.). Soil quality, seedling emergence, seedling survival, initial seedling growth and total seedling dry mass were measured after one year. We found higher seed emergence and seedling survival by combining LA soil with LA seeds or HA soil with HA seeds. Seedlings from LA seeds with both soil origins and seedlings from HA seeds with LA soils allocated more biomass to roots than seedlings from HA sites growing in HA soils under drier and warmer conditions. These results support the idea that autochthonous provenances have the potential to adapt to changing climatic conditions in their habitats.     

Ecdysone-dependent changes in the activity of ontogenetic puffs in the salivary glands of Drosophila cultivated in vitro as regards the effect of heterosis and selection of adaptively significant characters]

Regression of 4 intermolt and induction of 14 early ecdysone puffs in two inbred stocks of Drosophila with high (HA) and low (LA) activity and hybrid F1 HA x LA were studied. Experiments were performed in vitro with ecdysone-containing media. Differences in developmental rate and fitness of stocks HA, LA and their hybrid were shown to correlate with the rate of change in polythene chromosomes puffing activity. Adaptive heterosis and ontogenetic homeostasis mechanisms are under discussion in connection with the results obtained.     

Effect of ethanol on the levels of dopamine and its metabolites in the brain of rats with different degree of sensitivity to stress

It was shown, that content of dopamine and its metabolites (DOPAC and HVA) are the same in two groups of rats with different time of immobilization in forced swimming test. One group of low active (LA) animals experienced the immobilization more than 300s, other high active (HA) rats for less than 120 s. Ethanol (2 g/kg per oris) increased the level of DA in the striatum and medial prefrontal cortex only in LA rats and besides, the concentration of dopamine after ethanol administration was higher in the n. accumbens of LA rats, than in that of HA rats. The authors suggest that differences in dopamine content between LA and HA rats are connected with different levels of voluntary alcohol consumption. The opportunity to use both groups of HA and LA rats for developing models of pathogenic heterogeneity of alcoholism is discussed.     

High production of hyaluronic and lactic acids by Streptococcus zooepidemicus in fed-batch culture using commercial and marine peptones from fishing by-products

The combined production of biomass, hyaluronic acid (HA) and lactic acid (LA) in a glucose fed-batch system was studied. The complex culture media used were formulated with commercial and residual peptones from fish by-products. In all cases, fed-batch fermentations increased the productive period of HA and LA. Tryptone led to the highest productions but with the peptones from shark by-products similar LA concentrations and prominent HA levels were reached. Moreover, with this residual peptone higher molecular weight of HA were achieved. On the other hand, the equations proposed adjusted with accuracy and high statistical robustness the experimental kinetic profiles.     

Neuroplasticity in nucleus tractus solitarius neurons after episodic ozone exposure in infant primates.

Acute ozone exposure evokes adverse respiratory responses, particularly in children. With repeated ozone exposures, however, despite the persistent lung inflammation and increased sensory nerve excitability, the central nervous system reflex responses, i.e., rapid shallow breathing and decreased lung function, adapt, suggesting changes in central nervous system signaling. We determined whether repeated ozone exposures altered the behavior of nucleus tractus solitarius (NTS) neurons where reflex respiratory motor outputs are first coordinated. Whole cell recordings were performed on NTS neurons in brain stem slices from infant monkeys exposed to filtered air or ozone (0.5 ppm, 8 h/day for 5 days every 14 days for 11 episodes). Although episodic ozone exposure depolarized the membrane potential, increased the membrane resistance, and increased neuronal spiking responses to depolarizing current injections (P < 0.05), it decreased the excitability to vagal sensory fiber activation (P < 0.05), suggesting a diminished responsiveness to sensory transmission, despite overall increases in excitability. Substance P, implicated in lung and NTS signaling, contributed to the increased responsiveness to current injections but not to the diminished sensory transmission. The finding that NTS neurons undergo plasticity with repeated ozone exposures may help to explain the adaptation of the respiratory motor responses.     

Electrical connections between left superior pulmonary vein, left atrium, and ligament of Marshall: implications for mechanisms of atrial fibrillation

The importance of the ligament of Marshall (LOM) to rapid activations within the left superior pulmonary vein (LSPV) during atrial fibrillation (AF) remains poorly understood. We aimed to characterize the importance of electrical coupling between the LSPV with the left atrium (LA) and the LOM in the generation of high-frequency activations within this PV. We performed high-density mapping of the LSPV-LA-LOM junction in eight dogs, using 1,344 electrodes with a 1-mm resolution before and after posterior ostial ablation to diminish PV-LA electrical connections. A LOM potential was recordable up to 6.5 mm (SD 2.2) into the LSPV in all dogs during sinus rhythm (SR) and LA pacing. Functional LOM-LSPV electrical connections bypassing the PV-LA junction were present in five of eight dogs. Direct LOM-LSPV connections contributed to 46.5% (SD 16.0) of LSPV activations during AF, resulting in a greater propensity to develop focal activations (P < 0.05) and a higher activation rate during AF of LSPVs with direct LOM connections compared with those without (P < 0.03). Posterior LSPV ostial ablation without damaging the anterior wall or LOM slowed residual LA-PV conduction (P < 0.001). This diminished PV-LA coupling prevented the reinduction of LSPV focal activations in all dogs. However, persistent LOM focal activations in two dogs continued to activate the LSPV rapidly [cycle length 151.8 ms (SD 4.8)] via direct LOM-LSPV connections. LOM-LSPV connection forms an accessory pathway that contributes to the electrical coupling between LSPV and LA during SR and AF. This pathway may contribute to rapid activations within the LSPV during AF.     

Heterogeneity of Ca2+ gating of skeletal muscle and cardiac ryanodine receptors.

The single-channel activity of rabbit skeletal muscle ryanodine receptor (skeletal RyR) and dog cardiac RyR was studied as a function of cytosolic [Ca2+]. The studies reveal that for both skeletal and cardiac RyRs, heterogeneous populations of channels exist, rather than a uniform behavior. Skeletal muscle RyRs displayed two extremes of behavior: 1) low-activity RyRs (LA skeletal RyRs, approximately 35% of the channels) had very low open probability (Po < 0.1) at all [Ca2+] and remained closed in the presence of Mg2+ (2 mM) and ATP (1 mM); 2) high-activity RyRs (HA skeletal RyRs) had much higher activity and displayed further heterogeneity in their Po values at low [Ca2+] (< 50 nM), and in their patterns of activation by [Ca2+]. Hill coefficients for activation (nHa) varied from 0.8 to 5.2. Cardiac RyRs, in comparison, behaved more homogeneously. Most cardiac RyRs were closed at 100 nM [Ca2+] and activated in a cooperative manner (nHa ranged from 1.6 to 5.0), reaching a high Po (> 0.6) in the presence and absence of Mg2+ and ATP. Heart RyRs were much less sensitive (10x) to inhibition by [Ca2+] than skeletal RyRs. The differential heterogeneity of heart versus skeletal muscle RyRs may reflect the modulation required for calcium-induced calcium release versus depolarization-induced Ca2+ release.     

Oxygen debt in submaximal and supramaximal exercise in children at high and low altitude

The effect of high altitude (HA) on O2 debt and blood lactate concentration [( L]) was examined in 10- to 13-yr-old children who exhibited the same level of physical fitness. Fifty-one children acclimatized to HA (3,700 m) were compared with 40 children living at low altitude (LA, 330 m) during submaximal (20-95% maximal aerobic power, MAP), maximal and supramaximal (115% MAP) bicycle exercise. Results showed that 1) maximal O2 uptake (VO2max) and maximal heart rate were significantly (P less than 0.001) lower at HA than at LA by 15% and 11 beats X min-1, respectively; 2) for a given absolute work load, O2 debt was higher at HA than at LA, and the slopes of the linear relationships between O2 debt and O2 uptake were significantly higher at HA; 3) when related to percent of VO2max, O2 debts in HA and LA were similar; for 115% MAP maximal O2 debt and [L] were not significantly different (maximal O2 debt, 45.7 +/- 2.7 and 45.9 +/- 3.8 ml X kg-1; [L], 6.0 +/- 0.3 and 6.7 +/- 0.5 mM); and 4) linear relationships between maximal O2 debt and [L] were the same at HA and LA. This suggests that HA did not modify the anaerobic capacity in children.