Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min^?1 kg^?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.     

Dog-associated risk factors for human plague

Plague is a rare but often fatal zoonosis endemic to the western United States. Previous studies have identified contact with pets as a potential risk factor for infection. We conducted a matched case-control study to better define the risks associated with pets at both the household and individual levels. Using a written questionnaire, we surveyed nine surviving plague patients, 12 household members of these patients, and 30 age- and neighbourhood-matched controls about household and individual exposures. Overall, 79% of households had at least one dog, 59% had at least one cat and 33% used flea control, with no significant differences between case and control households. Four (44%) case households reported having a sick dog versus no (0%) control households [matched odds ratio, (mOR) 18.5, 95% confidence interval (CI) 2.3-infinity], and four (44%) patients reported sleeping in the same bed with a pet dog versus three (10%) controls (mOR 5.7, 95% CI 1.0-31.6). Within case households with multiple members, two (40%) of five patients slept with their dogs versus none (0%) of 12 healthy family members (P=0.13). The exposures to cats were not significant. Sleeping in the same bed as a pet dog remained significantly associated with infection in a multivariate logistic regression model (P=0.046). Our findings suggest that dogs may facilitate the transfer of fleas into the home and that activities with close extended contacts with dogs may increase the risk of plague infection.     

What determines the spatial extent of landscape effects on species?

Context

Landscape ecologists are often interested in measuring the effects of an environmental variable on a biological response; however, the strength and direction of effect depend on the size of the area within which the environmental variable is measured. Thus a central objective is to identify the optimal spatial extent within which to measure the environmental variable, i.e. the “scale of effect”.

Objectives

Our objectives are (1) to provide a comprehensive summary of the hypotheses concerning what determines the scale of effect, (2) to provide predictions that can be tested in empirical studies, and (3) to show, with a review of the literature, that most of these predictions have so far been inadequately tested.

Methods

We propose 14 predictions derived from five hypotheses explaining what determines the scale of effect, and review the literature (if any) supporting each prediction. These predictions involve five types of factors: (A) species traits, (B) landscape variables, (C) biological responses (e.g. abundance vs. occurrence), (D) indirect influences, and (E) regional context of the study. We identify methodological issues that hinder estimation of the scale of effect.

Results

Of the 14 predictions, only nine have been tested empirically and only five have received some empirical support. Most support is from simulation studies. Empirical evidence usually does not support predictions.

Conclusions

The study of the spatial scale at which landscape variables influence biological outcomes is in its infancy. We provide directions for future research by clarifying predictions concerning the determinants of the scale of effect.

     

Pathogenicity studies with the fungi Aphanomyces invadans, Achlya bisexualis, and Phialemonium dimorphosporum: induction of skin ulcers in striped mullet

Based on isolations from naturally infected fish in Florida, we investigated the role of the fungi Aphanomyces invadans, Achlya bisexualis, and Phialemonium dimorphosporum in the etiology of ulcerative mycosis (UM) in striped mullet Mugil cephalus. We injected healthy striped mullet subcutaneously with secondary zoospores of four oomycete isolates: two concentrations (50 and 115 zoospores/mL) of SJR (an endemic isolate of Aphanomyces invadans in American shad Alosa sapidissima from the St. Johns River); two concentrations each of CAL (25 and 65 zoospores/mL) and ACH (1,400 and 2,000 zoospores/mL; endemic isolates of Aphanomyces invadans and Achlyva bisexualis, respectively, in striped mullet from the Caloosahatchee River); and two concentrations of the ascomycete culture MTZ (2,500 and 3,500 zoospores/mL; endemic isolate of P. dimorphosporum from whirligig mullet M. gyrans in the Matanzas Inlet). All fish injected with either concentration of SJR developed granulomatous ulcers after 8 d and died within 21 d. Eighty percent (8/10) of fish injected with the high dose of CAL developed ulcers after 13 d and died within 28 d, but only 30% (3/10) of fish injected with the low dose of CAL developed ulcers. Four of the ulcerated fish died within 28 d, and the remaining fish were terminated after 32 d. Fish injected with zoospores of Aphanomyces invadans developed ulcers that were grossly and histologically similar to those observed in naturally infected striped mullet with UM from several estuaries or rivers in Florida. These hemorrhagic skin ulcers were characterized by myonecrosis and the presence of mycotic granulomas. None of the fish injected with ACH, MTZ, or sterile water developed ulcers. This study fulfilled Koch's postulates and demonstrated that ulcers could be experimentally induced in striped mullet after exposure via injection to secondary zoospores of an endemic Florida strain of Aphanomyces invadans.     

Enhancing capacity for freshwater conservation at the genetic level: a demonstration using three stream macroinvertebrates

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Gonadal Stage and Sex Steroid Correlations in Siberian Sturgeon,Acipenser baeri,Habituated to a Semitropical Environment

Stages of gonadal development, in association with plasma concentrations of the sex steroids 17β‐estradiol (E2), progesterone (P4), testosterone (T), and 11‐ketotestosterone (11‐KT), were investigated for a single time point during a natural breeding season in 7‐yr‐old Siberian sturgeon, Acipenser baeri Brandt, exposed lifelong to a warmwater environment. Among females, examination of gonadal tissue showed variation in ovarian stage, with 12.5, 47.5, 22.5, and 17.5% of females found at Stages 2 (previtellogenic), 3 (early vitellogenic), 4 (mid‐vitellogenic), and 5 (migratory nucleus), respectively. Although patterns varied among the hormones, plasma concentrations of E2, T, and 11‐KT became increasingly elevated in females as maturation progressed. On the basis of histological criteria, males were classified as either premeiotic (quiescent) or meiotic and 50% of the males sampled were found at each stage. Significant elevations in circulating concentrations of plasma E2 and T were observed in meiotic versus premeiotic males, and there was a rise in plasma 11‐KT concentration that approached significance (P = 0.056).     

Longitudinal variations in exposed riverine sediments: a context for the ecology of the Fiume Tagliamento,Italy

1. A key component of physical habitat along braided river systems is the exposed riverine sediment within the active zone. The relatively unmanaged, gravel‐bed Fiume Tagliamento, Italy, provides the focus for exploring two ecologically important properties of exposed riverine sediments: their within‐patch and between‐patch variability in calibre. 2. To characterize between‐patch variation in exposed riverine sediments, replicate (within‐patch) samples were obtained from three geomorphologically distinct locations along 130 km of the river: bar heads along the margin of the low‐flow channel, the heads of major bars across the exposed surface of the active zone, and floodplain surfaces. A photographic technique enabled rapid and consistent field sampling of the coarse sediments at bar heads along the low‐flow channel margin and on major bars across the dry bed. 3. A downstream decrease in particle size and an increase in within‐patch heterogeneity in sediment size were observed within bar head sediments along the margin of the low‐flow channel. Comparisons between major bar and low‐flow channel samples revealed greatest within‐patch variability in individual sediment size indices (D₅₀, A‐ and B‐axes of the larger particles) at headwater sites, greatest between‐patch variability in the three measured indices in the central reaches, and lowest between‐patch variability at downstream sites. However, there was a distinct increase in the overall heterogeneity in particle size, which was sustained across all patches, in a downstream direction. 4. There was a clear downstream decrease in the size of floodplain sediments in the headwaters, but thereafter there was no distinct downstream trend in any of the calculated particle size indices. 5. The geomorphological controls on the observed patterns and the potential ecological significance of the patterns, particularly for plant establishment, are discussed in relation to the relative relief of the active zone, and the highly variable hydrological and climatic regime along the river. Copyright © 2000 John Wiley & Sons, Ltd.