Rates of accumulation of dieldrin by a freshwater filter feeder: Sphaerium corneum.

The rate of dieldrin accumulation by Sphaerium corneum was determined in the field and under controlled conditions in the laboratory. The methods gave comparable results and it was established that Sphaerium attained an equilibrium concentration of dieldrin in its tissues in a short time period and exhibited a bioaccumulation factor of 1000. The rate of dieldrin accumulation by direct uptake from dieldrin in solution was compared to the rate obtained for indirect uptake from dieldrin adsorbed onto particulate material. The primary route of dieldrin uptake into Sphaerium was shown to be by direct partitioning of residues into lipoidal tissues from water. The effect of temperature on the rate of accumulation was also studied. The rate of accumulation increased with temperature in the range 5 degrees C to 20 degrees C. The frequency of gill cilia beat in relation to accumulation rate was studied in this temperature range and a correlation is shown.

Non-invasive determination of instantaneous heart rate in developing avian embryos by means of acoustocardiogram.

Previous noninvasive studies of the mean heart rate of embryonic birds have prompted an investigation into the instantaneous heart rate (IHR), which may be informative in developmental studies of cardiac rhythm. Using the acoustocardiogram (ACG), a noninvasive, long-term measuring system for embryonic IHR is developed, and the IHR in chickens during the last half of embryonic development is determined. The system, which uses a micro-computer, samples the ACG at a frequency of 50 Hz, restores the ACG wave by sinc function and calculates the IHR with an error in accuracy of less than 1 beat min-1. It was found that characteristic, transient bradycardia begins to appear late in the second week of incubation, and, with the additional development of transient tachycardia, the embryonic cardiac rhythm becomes more arrhythmic towards hatching. Simultaneous measurements of IHR with somatic movements showed no relationship between arrhythmia and embryonic activities. This system is useful, providing new evidence on long-term IHR developmental patterns.

Ballistocardiogram of avian eggs determined by an electromagnetic induction coil.

As an avian embryo grows within an eggshell, the whole egg is moved by embryonic activity and also by the embryonic heartbeat. A technical interest in detecting minute biological movements has prompted the development of techniques and systems to measure the cardiogenic ballistic movement of the egg or ballistocardiogram (BCG). In this context, there is interest in using an electromagnetic induction coil (solenoid) as another simple sensor to measure the BCG and examining its possibility for BCG measurement. A small permanent magnet is attached tightly to the surface of an incubated egg, and then the egg with the magnet is placed in a solenoid. Preliminary model analysis is made to design a setup of the egg, magnet and solenoid coupling system. Then, simultaneous measurement with a laser displacement measuring system, developed previously, is made for chicken eggs, indicating that the solenoid detects the minute cardiogenic ballistic movements and that the BCG determined is a measure of the velocity of egg movements.

Exogenous ghrelin accentuates the acute hypoxic ventilatory response after two weeks of chronic hypoxia in conscious rats.

AIM: Ghrelin has been implicated as a modulator of numerous physiological pathways. To date, there have not been any studies describing the role of ghrelin in modulating the chemoreflex control of pulmonary ventilation. Yet the respiratory system impacts, at least to some degree, on virtually all homeostatic control systems. Chronic hypoxia (CH) can cause fundamental changes in ventilatory control, evident by alterations in the acute hypoxia ventilatory response (HVR). As ghrelin plays an important role in metabolic homeostasis, which is tightly linked to ventilatory control, we hypothesized that ghrelin may modulate HVR, especially following CH. METHODS: Whole body plethysmography was used to measure the HVR (8% O(2) for 10 min) in male Sprague-Dawley rats (body wt ∼180-220 g) before and after 14 days of CH (CH=10% O(2)). During CH, rats received daily subcutaneous injections of either saline (control; n=5) or ghrelin (150 µg kg(-1) day(-1); n=5). The HVR was measured in another four rats that had received daily injections of ghrelin during normoxia for 7 days. RESULTS: Ghrelin did not significantly alter basal ventilatory drive or acute HVR in normoxic rats. However, the acute HVR was accentuated following CH in ghrelin-treated rats compared with saline-treated rats. CONCLUSIONS: These results describe the impact that ghrelin has in altering ventilatory control following CH and, although the mechanisms remain to be fully elucidated, provide guidance for future ghrelin-based studies interpreting physiological data indirectly related to the chemoreflex control of pulmonary ventilation.

Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements.

Usnic acid is a component of nutritional supplements promoted for weight loss that have been associated with liver-related adverse events including mild hepatic toxicity, chemical hepatitis, and liver failure requiring transplant. To determine if metabolism factors might have had a role in defining individual susceptibility to hepatotoxicity, in vitro metabolism studies were undertaken using human plasma, hepatocytes, and liver subcellular fractions. Usnic acid was metabolized to form three monohydroxylated metabolites and two regio-isomeric glucuronide conjugates of the parent drug. Oxidative metabolism was mainly by cytochrome P450 (CYP) 1A2 and glucuronidation was carried out by uridine diphosphate-glucuronosyltransferase (UGT) 1A1 and UGT1A3. In human hepatocytes, usnic acid at 20 microM was not an inducer of CYP1A2, CYP2B6, or CYP3A4 relative to positive controls omeprazole, phenobarbital, and rifampicin, respectively. Usnic acid was a relatively weak inhibitor of CYP2D6 and a potent inhibitor of CYP2C19 (the concentration eliciting 50% inhibition (IC(50)) = 9 nM) and CYP2C9 (IC(50) = 94 nM), with less potent inhibition of CYP2C8 (IC(50) = 1.9 microM) and CYP2C18 (IC(50) = 6.3 microM). Pre-incubation of microsomes with usnic acid did not afford any evidence of time-dependent inhibition of CYP2C19, although evidence of slight time-dependent inhibition of CYP2C9 (K(I) = 2.79 microM and K(inact) = 0.022 min(-1)) was obtained. In vitro data were used with SimCYP(R)to model potential drug interactions. Based on usnic acid doses in case reports of 450 mg to >1 g day(-1), these in vitro data indicate that usnic acid has significant potential to interact with other medications. Individual characteristics such as CYP1A induction status, co-administration of CYP1A2 inhibitors, UGT1A1 polymorphisms, and related hyperbilirubinaemias, or co-administration of low therapeutic index CYP2C substrates could work alone or in consort with other idiosyncrasy risk factors to increase the risk of adverse events and/or hepatotoxicity. Thus, usnic acid in nutritional supplements might be involved as both victim and/or perpetrator in clinically significant drug-drug interactions.

Does central nitric oxide chronically modulate the acute hypoxic ventilatory response in conscious rats?

AIM: Hypoxia initiates an increase in ventilation (VE) through a cascade of events of which central nitric oxide (NO) has been implicated as an important neuromodulator. There have not been any reports describing the consequences of long-term imbalances in the central NO pathways on the modulation of the acute hypoxic ventilatory response (HVR). Chronic hypoxia (CH) can potentially modify the HVR, and so we hypothesized that central NO may be involved. In this study we describe the long-term role of central NO in the modulation of HVR before and after CH. METHODS: Male Sprague-Dawley rats (BW c. 200-320 g; n = 21) were implanted with an osmotic pump for continuous intracerebroventricular administration of either artificial cerebrospinal fluid (control), Nomega-nitro-L-arginine methyl ester (L-NAME) (150 microg kg(-1) day(-1)) or the NO-donor, 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1) (100 microg kg(-1) day(-1)). The VE response to acute poikilocapnic hypoxia (8% O2 for 20 min) was measured by plethysmography seven days after surgery, in normoxia, and again after 14 days of exposure to CH (CH = 12% O2). RESULTS: The magnitude of the HVR (c. 230% increase in VE) was unaltered by centrally infusing either L-NAME or SIN-1 for 1 week. CH did not modify the HVR, although baseline VE and HVR were shifted downward by L-NAME during CH - because of a reduction in the frequency component. CONCLUSIONS: These results suggest that long-term alterations in central NO levels may not alter the HVR under moderate CH, presumably because of the onset/development of compensatory mechanisms. However, NO appears to be an important component of the HVR following CH.

An allometric study of lung morphology during development in the Australian pelican, Pelicanus conspicillatus, from embryo to adult.

Pelicans produce altricial chicks that develop into some of the largest birds capable of sustained flight. We traced pulmonary morphological development in the Australian pelican, Pelicanus conspicillatus, from third trimester embryos to adults. We described growth and development with allometric relationships between lung components and body mass or lung volume, according to the equation y = ax(b). Pelican lung volume increased faster than body mass (b = 1.07). Relative to lung volume, the airways and vascular spaces increased allometrically (b > 1) in embryos, but isometrically (b approximately 1) after hatching. Parabronchial mantle volume decreased (b < 1) prior to hatching and increased isometrically thereafter. Surface area of air capillaries, blood capillaries and the blood-gas barrier increased relative to lung volume (b > 0.67) before and after hatching. Barrier thickness decreased before hatching, remained constant in juveniles and decreased by adulthood. The anatomical diffusing capacity significantly increased before hatching (b = 4.44) and after hatching (b = 1.26). Although altricial pelicans developed pulmonary complexity later than precocial turkeys, the volume-specific characteristics were similar. However, lungs of volant adult pelicans became significantly larger, with a greater capacity for gas exchange, than lungs of terrestrial turkeys. Exchange characteristics of growing pelican lungs were inferior to those of adult birds of 26 other species, but converged with them at maturity.

Oxygen consumption rates of adults and chicks during brooding in king quail (Coturnix chinensis).

Oxygen consumption rates were measured in chicks (0-17 days of age), and in non-brooding and brooding adults. Brooded chicks maintained a constant oxygen consumption rate at a chamber ambient temperature of 10-35 degrees C (0-5 days of age: 2.95 ml O2.g-1.h-1 and 6-17 days of age: 5.80 ml O2.g-1.h-1) while unbrooded chicks increased oxygen consumption rate at ambient temperature below 30 degrees C to double the brooded oxygen consumption rate at 25 and 15 degrees C for chicks < 5 days of age and > 5 days of age, respectively. The mass-specific oxygen consumption rate of breeding male and females (non-brooding) were significantly elevated within the thermoneutral zone thermal neutral zone (28-35 degrees C) in comparison to non-breeding adults. Below the thermal neutral zone, oxygen consumption rate was not significantly different. The elevation in oxygen consumption rate of breeding quail was not correlated with the presence of broodpatches, which developed only in females, but is a seasonal adjustment in metabolism. Male and females that actively brooded one to five chicks had significantly higher oxygen consumption rate than nonbrooding quil at ambient temperature below 30 degrees C. Brooding oxygen consumption rate was constant during day and night, indicating a temporary suppression of the circadian rhythm of metabolism. Brooding oxygen consumption rate increased significantly with brood number, but neither adult body mass nor adult sex were significant factors in the relationship between brooding oxygen consumption rate and ambient temperature. The proportion of daylight hours that chicks were brooded by parents was negatively correlated with ambient temperature. After chicks were 5 days old brooding time was reduced but brooding oxygen consumption rate was unchanged. Heat from the brooding parent appeared to originate mainly from the apteria under the wings and legs rather than the broodpatch. The parental heat contribution to chick temperature regulation below the chicks' thermal neutral zone is achieved by increasing parental thermal conductance by a feedback control similar to that suggested for the control of egg temperature via the broodpatch. It is concluded that the brooding period is an energetic burden to parent quail, and the magnitude of the cost increases directly with brood number and inversely with ambient temperature during this period.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of thermoregulation and posthatching growth in the altricial cockatiel Nymphicus hollandicus.

The development of thermoregulation and growth during the nestling period of cockatiel Nymphicus hollandicus were examined in this study. It was hypothesised that, in comparison to other altricial species of similar body mass, cockatiel chicks develop endothermy earlier and consequently have less energy available for growth, resulting in reduced growth rates. While poorly insulated and blind at hatching, cockatiel developed endothermic responses in their first week, and were individually effectively homeothermic (with 75% of adult ability to maintain body temperature during exposure to 20 degrees-25 degrees C), by maintaining high metabolic rates (at all ambient temperatures tested) above the predicted resting rates of an adult of similar body mass before parental brooding ceased (12-13 d). Mass-independent metabolic rates were equivalent to those of fledglings at only 20% of the nestling period (37 d), well before adequate insulation was obtained. The Gompertz growth constants of cockatiel were significantly lower than those of other altricial land birds, which supports the hypothesis of this study.

Development of cardiac rhythms in altricial avian embryos.

Mean heart rate (MHR) was determined during incubation and in hatchlings of 14 altricial avian species to investigate (1) if there is a common developmental pattern of heart rate in altricial embryos and (2) if heart rate changes during incubation are correlated with changes in embryonic growth rate. On the basis of normalized incubation MHR increased approximately linearly in 12 of 14 species from as early as 30-40% of incubation to that of pipped embryos. The MHR of hatchlings was equal to or higher than that of pipped embryos in seven species. Passerine embryos and hatchlings maintained higher MHR in comparison to parrots of similar egg mass, which may reflect phylogenetic differences in development. Embryonic MHR increased at a higher rate while embryonic growth rates were highest during the first 40% of incubation in tit, budgerigar and crow embryos than during subsequent development when relative growth rates decreased. MHR became independent of yolk-free wet mass at a smaller fraction of hatchling mass in budgerigar and crow than in the tit, suggesting that MHR is more likely to increase continuously after 40% of incubation in small altricial species than larger species.