Opioid receptor types in the brain of the Afghan pika (Ochotona rufescens), a species which is naturally tolerant to morphine

The rabbit is normally sensitive to morphine while another lagomorph, the Afghan pika Ochotona rufescens is naturally tolerant to the analgesic effects elicited by the opium alkaloid. In spite of the different responsiveness of the two species to morphine we find that the pika brain and the rabbit brain both contain a mixture of mu-, delta- and kappa-opioid sites in nearly the same proportions: 46-47% mu, 23% delta and 28-30% kappa. Moreover, apparent binding of morphine in pika and rabbit brain membranes is inhibited in the presence of Na+ ions and/or of 5-guanylylimidodiphosphate indicating that morphine should behave as an opiate agonist (analgesic) not only in rabbits, which it does but also in pikas, which it does not. Taken together these results suggest that the natural tolerance of the Afghan pika to morphine may not reside in modified opioid receptor types and that its origin should be sought elsewhere.     

Effect of ghrelin in dry matter intake and energy metabolism in prepartum sheep: a preliminary study

The objective of this study was to determine the effect of ghrelin on dry matter intake and energy metabolites in ewes during the last 10d of gestation. Ewes were randomly assigned to either a treatment (n=6) or a control group (n=6). One hour after feeding (08:00 and 16:00), ewes in the treated group were given ovine ghrelin (3 microg/kg, i.m.) and the control group received an equivalent volume of saline. Treatments were continued until lambing. Daily blood samples were taken starting at assignment. The principal findings were that: (1) ewes treated with ghrelin had a higher dry matter intake only on the first day of treatment; (2) treated ewes had lower serum concentrations of non-esterified fatty acids and insulin but higher serum concentrations of growth hormone; (3) serum concentrations of beta-hydroxy butyrate and cortisol were not different between treated and non-treated ewes. In conclusion, treatment with ghrelin affected dry matter intake and energy metabolites of pre-partum ewes during the last 10 d of pregnancy.     

Science in drug control: the alkaloid content of afghan opium

Opium samples from Afghanistan were analyzed by HPLC for their content of morphine and three further alkaloids (codeine, thebaine, and papaverine). To our knowledge, this is the largest set of authentic opium samples analyzed in one study until now. The purpose was to assess possible correlations between samples and selected external factors, such as region of origin within Afghanistan, year of harvest, or intra-batch variation. In the investigated samples, a trend towards higher morphine concentrations in opium from the North-Eastern parts of Afghanistan was observed in the period from 2003 to 2005. More than 75% of the samples contained above 10% of morphine, the overall average was 14.4%.     

Salivary cues in the mouse: a preliminary study

Two experiments were designed to explore the possible role of mouse saliva in modulating social interactions. Experiment 1 examined the investigatory sniffing behavior of an intact male toward either another intact male or castrated male. It was found that castrates received more mouth, ears-eyes, and hind sniffing than intacts. In addition, the temporal patterning of mouth and ears-eyes sniffing was found to be different for the two stimulus conditions. The findings of Experiment 2 indicated that saliva from testosterone-treated castrates contained aggression-promoting cues relative to saliva from castrated control animals. Possible sources of the salivary chemosignal were discussed.     

Long-term dynamics in a metapopulation of the American pika

A 20-yr study of a metapopulation of the American pika revealed a regional decline in occupancy in one part of a large network of habitat patches. We analyze the possible causes of this decline using a spatially realistic metapopulation model, the incidence function model. The pika metapopulation is the best-known mammalian example of a classical metapopulation with significant population turnover, and it satisfies closely the assumptions of the incidence function model, which was parameterized with data on patch occupancy. The model-predicted incidences of patch occupancy are consistent with observed incidences, and the model predicts well the observed turnover rate between four metapopulation censuses. According to model predictions, the part of the metapopulation where the decline has been observed is relatively unstable and prone to large oscillations in patch occupancy, whereas the other part of the metapopulation is predicted to be persistent. These results demonstrate how extinction-colonization dynamics may produce spatially correlated patterns of patch occupancy without any spatially correlated processes in local dynamics or extinction rate. The unstable part of the metapopulation gives an empirical example of multiple quasi equilibria in metapopulation dynamics. Phenomena similar to those observed here may cause fluctuations in species' range limits.     

Breast compression: a preliminary study

X-Ray mammography is the technique employed to image breast tumours; it is the gold standard for both diagnosis and screening¹. To increase the sensitivity of the test and to reduce the dose of X-radiation, breast compression is used. The effect of squeezing a simple model of a breast in which there is an idealized spherical tumour volume is investigated; the cases where the lesion has both a smaller, and a larger compressibility than the surrounding tissues are considered. Surface strain is computed as a function of the deformation of the lesion from its spherical shape. Evidence from earlier studies is adduced to show that when the lesion is malignant care should be exercised to avoid the possibility of disseminating cancer cells by the application of compressive forces.     

Comparative study of red-cell enzyme polymorphism in the pika and the rabbit

The variants of seven red-cell enzyme systems of two families of Lagomorphae (rabbit and pika) are studied by enzymoelectrophoretic determination of isoenzyme distribution.
Polymorphism appears in five different enzymes (PGM, AK, G6PD, 6PGD and NADH diaphorase) in the pika and in one system (NADH diaphorase) in the rabbit. The electropherograms of acid phosphatase and LDH do not show any variability in either pikas or rabbits. In the pika, red-cell enzyme polymorphism is as intense as it is in man.     

Morphine metabolism revisited: I. Metabolic activation of morphine to a reactive species in rats

Treatment of fasted rats with relatively high doses of morphine rapidly results in depletion of hepatic glutathione (GSH) content and marked elevation of serum transaminase activity. Such morphine-induced response has been generally attributed to central nervous system mediated effects of the drug. We now report that this response might be due to a direct effect of the drug in the liver. That is, its metabolic activation to reactive electrophilic metabolite(s), by the hepatic cytochrome P-450-dependent mixed function oxidase system. Structure-activity relationships of morphine and its congeners indicate that the (-)-3-hydroxy-N- methylmorphinan moiety is linked with the potential of these opioids to deplete hepatic GSH and to raise serum transaminases in rats.     

Morphine metabolism and normorphine in Papaver somniferum

Normorphine has been established as an active metabolite of morphine in P. somniferum. This was done by, (a) demonstrating the presence of normorphine throughout the life cycle of the plant, (b) finding normorphine-¹⁴C after feeding morphine-¹⁴C via the roots, and (c) exposing opium poppies to ¹⁴CO₂ under steady state conditions which led to morphine and normorphine of the same specific activity. Feeding normorphine-¹⁴C showed that the N-demethylation step is irreversible. A sensitive procedure was developed for the detection of normorphine in the presence of large amounts of morphine; using this procedure, normorphine was found in raw opium. These results indicate that the major, if not the sole, morphine degradative pathway involves an initial demethylation to normorphine, which is subsequently degraded to non-alkaloidal metabolites. The high rates of turnover observed led to the conclusion that the morphine alkaloids do play an active metabolic role, perhaps as specific methylating agents.     

Estrogen metabolism, not biosynthesis, in rabbit articular cartilage and isolated chondrocytes: a preliminary study.

Because serum estrogen levels are associated with the presence of osteoarthritis, and cartilage tissue is known to contain estrogen receptors, it is of interest to determine the extent to which estrogen is biosynthesized and/or metabolized in cartilage tissue or isolated chondrocytes. In this preliminary study, using a sensitive assay method, estrogen synthetase (aromatase) was undetectable in articular cartilage or isolated chondrocytes in culture from immature female rabbits. However, estrogen metabolism, specifically estrogen 17 beta-hydroxysteroid dehydrogenase activity, was detected in homogenized cartilage tissue, and at substantially higher specific activities in freshly isolated chondrocytes. These fresh chondrocytes, assayed in culture without any exogenous cofactor, demonstrated a significantly higher activity for converting the weak estrogen, estrone, to the more potent estrogen, estradiol. Chondrocytes grown to confluence in culture had very low estrogen 17 beta-hydroxysteroid dehydrogenase specific activity. Homogenized cartilage tissue, tested only with added NADPH as cofactor, also showed a preference for estradiol as the principal product, but this may have been primarily due to the use of reduced cofactor. If subsequent experiments confirm the presence of estrogen 17 beta-hydroxysteroid dehydrogenase activity, and its preference for converting estrone into estradiol, in human cartilage tissue and chondrocytes, this could have substantial implications in the estrogen dependency of osteoarthritis.     

Sheep lymphocyte antigens: a preliminary study

Sera from 287 sheep were screened for cytotoxic antibodies against sheep lymphocytes. Forty four antisera were selected which provisionally define 13 lymphocyte antigens. The frequency of these antigens was studied in 305 sheep from 8 flocks of different breeds. Family studies confirm that inheritance of sheep lymphocyte antigens is controlled by the autosomal codominant genes of at least 2 linked loci.     

Morphine metabolism revisited. III. Confirmation of a novel metabolic pathway

Previous studies have led to the partial structural characterization of a glutathionylmorphine adduct which was isolated from rat liver microsomal incubations. The formation of this adduct was shown to be catalyzed by cytochrome P-450. As an extension of this work, we have carried out similar studies with N-acetylcysteine in an attempt to obtain a product amenable to complete NMR analysis and unambiguous structure assignment. Incubation of [3H]morphine and N-acetylcysteine with microsomal preparations isolated from human and from phenobarbital-treated rats led to the isolation by HPLC of a labeled species displaying a fast atom bombardment mass spectrum consistent with the expected N-acetylcysteinyl adduct of morphine. Data obtained from the high resolution 1H-NMR spectrum of the adduct and that of synthetic 10 alpha-hydroxycodeine established the structure of the metabolite as 10 alpha-S-(N-acetylcysteinyl)morphine. The results are consistent with the biotransformation of morphine involving oxidation at the benzylic C-10 position to form an electrophilic species capable of reacting with nucleophilic thiols such as N-acetylcysteine and glutathione.     

Habitat-specific demography: evidence for source-sink population structure in a mammal,the pika

Theory suggests that populations may persist in sink habitats that cannot support replacement-level birth rates. Although it is commonly believed that organisms that can actively select habitat should rarely occur in sinks, the frequency of use of sinks in free-ranging species is not well-documented. We found that a population of American pikas ( Ochotona princeps, Lagomorpha) inhabiting distinct alpine habitats (meadow and snowbed) in Wyoming, USA, had habitat-specific demographic rates that produced a source-sink population structure. Population size increased in both habitats in summer and declined in both habitats in winter, with populations in snowbeds increasing more during summer and decreasing more over winter. Birth rates were consistently higher in meadows and populations in meadows had a consistently higher finite rate of increase (lambda, from life tables) than did those in snowbeds, for which lambda was far below that needed for replacement. Patterns of immigration, population structure, and temporal variation in population size were as expected if meadows were functional sources and snowbeds functional sinks. Patterns of snowmelt differed between habitats, predicted the critical difference in birth rates between habitats, and are a likely primary cause of the differences in habitat-specific birth rates that we observed. This study provides a clear example of source-sink population structure for a mammal.     

Molded vascularized osteoneogenesis: a preliminary study in rabbits

The clinical application of free vascularized bone grafting techniques in reconstructive surgery has limitations with respect to available donor sites and configuration of the graft. In this study, we were able to produce a vascularized bone graft with a predetermined size and shape by the use of titanium chambers implanted into the groins of rabbits. Forty adult New Zealand white rabbits were included in this study. In all animals, bone fragments were harvested from the iliac crests and placed within a titanium chamber. The chamber was positioned in the groin with the saphenous vessels passing through the chamber longitudinally in contact with the bony fragments. In half the animals, a segment of periosteum was harvested from the tibia and sutured around the vessels with the cambium layer facing the bone fragments. Sacrifices were performed at 4, 8, 12, and 16 weeks to examine the chamber contents. At all time periods, the contents completely filled the chamber, and the saphenous vessels remained patent. Histologic evaluation showed remodeling of the bone fragments as early as 4 weeks concomitant with a sprouting vascular network demonstrable with microangiography. Fluorochrome bone labels documented new bone formation within the chamber. These changes were progressive to week 12, but the 16-week specimens appeared to be undergoing resorption.