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Biomedical subjects

M S Moss

Publications and source records attributed to M S Moss.

At least 37 records · Page 2Linked to original sources

The identification of C-18 neutral steroids in normal stallion urine.

As part of a continuing research program associated with the detection of anabolic steroid residues in horse urine, normal samples from entire male horses have now been investigated. Isomers of three C-18 neutral steroids; 4-estren-17-ol-3-one (1), estrane-3,17-diol (2) and an unsaturated estranediol having a possible structure (3), have been identified in urine samples from two male horses aged 8 and 14 years. Of these three steroids, compound (2) was not detected in the urine of a 2.5 yr old entire male nor in the majority of post-race urine samples from entire male horses average age 3.8 yrs (n = 34). Ten of these samples showed tentative indications of this compound. Although the isolation of isomers of estrane-3,17-diol from human non-pregnancy urine has been reported previously, analysis of non-pregnancy urine samples in the present study did not reveal the presence of these compounds.

Animals↗

Predictors of falls among institutionalized women with Alzheimer's disease.

Falls among elderly residents are a major concern of facilities caring for the aged. A group of institutionalized women with senile dementia of the Alzheimer type (N = 60; mean age 83) were studied longitudinally and evaluated annually on 21 variables of physical, social, emotional, self-care, and cognitive functioning. A substudy of falls they experienced used data from two such annual evaluations. Clinical ratings by the interdisciplinary team estimated 1) the women's changes in function during the preceding year and 2) the current levels of the women's functioning. Separate regressions for each of the two years returned identical significant patterns indicating that ratings of physical vigor were significantly related to number of falls. Those women who had been among the most vigorous in the group but who had shown significant declines in the preceding year were the most vulnerable to falls; women who had been rated as the least vigorous but whose levels of vigor had been stable during the year tended to have fewer falls. Falling therefore appears to be related to the process of decline in vigor among those in the group whose levels of vigor were higher initially. There were corresponding significant declines in emotional and cognitive scales.

Accidents↗

The fine structure of the caudal periaqueductal gray of the cat: morphology and synaptic organization of normal and immunoreactive enkephalin-labeled profiles.

Although the midbrain periaqueductal gray (PAG) is thought to have a major role in an endorphin-mediated analgesia system, little is known about its neuroanatomical organization. To determine the microcircuitry within the PAG through which exogenous and endogenous opiates may act, we analyzed the synaptic organization of normal and immunoreactive enkephalin (ENK)-labeled profiles in the caudal PAG, a region of particular interest because of its effectiveness in generating analgesia. Examination of the normal fine structure of this region demonstrated that there is no characteristic synaptic morphology that distinguishes individual regions of the caudal PAG (ventromedial, ventrolateral and dorsolateral) from one another. In all 3 regions of the caudal PAG, axodendritic synapses are the predominant form of synaptic interaction making up 93-97% of all synapses counted. Axosomatic synapses are much less common, as are presumed axoaxonic and dendrodendritic synapses. In the caudal ventral PAG, the largest population of ENK-labeled axonal boutons are found presynaptic to unlabeled, centrally placed dendrites. Much less frequently, immunoreactive ENK-containing boutons are found presynaptic to neuronal perikarya or vesicle-containing profiles. Thus, these results suggest that the dendrites of neurons intrinsic to the PAG are the most probable site of opiate action in the caudal ventral PAG.

Animals↗

The metabolism of fenclofenac in the horse.

14C-Fenclofenac (2-(2'-4'-dichlorophenoxy)-phenylacetic acid) was administered orally to horses, and urinary metabolites investigated by chromatography. Fenclofenac was rapidly absorbed and eliminated, with a plasma half-life (t1/2) of 2.3 h, with 83.2 and 85.8% of the dose being recovered in the urine in 0-24 h. The major urinary metabolite was the ester glucuronide (58.8, 70.0% dose), and evidence is presented that this metabolite undergoes a structural rearrangement to give beta-glucuronidase-resistant isomers. The other 14C-labelled components in horse urine were unchanged fenclofenac (13.1, 11.5% dose), and two minor metabolites, one of which was identified as a monohydroxy fenclofenac. This study is the first to show an ester glucuronide to be the major metabolite of a non-steroidal anti-inflammatory drug in the horse.

Animals↗

The peptidergic organization of the cat periaqueductal gray. II. The distribution of immunoreactive substance P and vasoactive intestinal polypeptide.

Despite the important contribution of the midbrain periaqueductal gray (PAG) to endogenous pain suppression systems, little is known about the neuroanatomical basis of its functional organization. In a previous study of the distribution of the endogenous opiate leucine-enkephalin (ENK) in the PAG (Moss, M. S., E. J. Glazer, and A. I. Basbaum (1983) J. Neurosci. 3: 603-616), we found that immunoreactive ENK-containing neurons and terminals are clustered in discrete populations. In this study we have extended our analysis of the neurochemical organization of the PAG by using immunocytochemistry to map the distribution of two non-opiate peptides that produce potent analgesia when administered at central gray levels: substance P (Sub P) and vasoactive intestinal polypeptide (VIP). Immunoreactive Sub P neurons and terminal fields are clustered in discrete populations throughout the PAG. The distribution pattern of these populations changes at different rostral-caudal levels of the PAG. For example, there is a ventral-to-dorsal shift in the location of Sub P-like immunoreactivity from the caudal to the rostral PAG. Few immunoreactive Sub P neurons are found in the nucleus raphe dorsalis although moderately dense terminal field staining is present. The staining pattern of immunoreactive VIP is totally different from that of Sub P. Regardless of the rostral-caudal level examined, VIP-containing neurons are found tightly clustered in the subependymal neuropil of the ventromedial PAG. Only a few immunoreactive VIP-containing neurons are found in the ventral PAG or nucleus raphe dorsalis. The striking differences between the distribution of Sub P- and VIP-like immunoreactivity in the PAG indicates that the neural circuitry underlying pain suppression by Sub P and VIP may also differ.

Animals↗

The peptidergic organization of the cat periaqueductal gray. I. The distribution of immunoreactive enkephalin-containing neurons and terminals.

Despite the significant contribution of the periaqueductal gray (PAG) to an endogenous pain suppression system, little is known about its neurochemical organization. Previous pharmacological and physiological studies have indicated regional variations in the effectiveness with which the midbrain PAG can generate potent analgesia in response to either opiate microinjection or electrical stimulation. There is, however, no anatomical correlate of this regional variation. As a first step toward elucidating the neural circuitry underlying the PAG's contribution to endogenous pain suppression systems, we have mapped the distribution of leucine enkephalin (ENK)-like immunoreactivity in the cat PAG. Throughout the rostral-caudal extent of the PAG, ENK-containing neurons are clustered in discrete populations. ENK terminal field staining is somewhat more diffuse; however, there are several regions where terminal staining is consistently more intense. The distribution of ENK perikarya and terminals undergoes a ventral to dorsal shift from caudal to rostral PAG. Conceivably, the clustered distribution of ENK cells and terminals contributes to the differential effectiveness of various PAG regions in generating analgesia. The ventral-dorsal shift of ENK immunoreactivity may (1) correspond to a somatotopic organization within the PAG or (2) mirror the topographic relationship of the PAG's interactions with other components of the endogenous analgesia system. In addition, the changing pattern of ENK immunoreactivity may also reflect the involvement of the PAG and of endogenous opiates in systems other than those of pain control.

Animals↗

3-Hydroxy- and 3-keto-3-phenylpropionic acids: novel metabolites of benzoic acid in horse urine.

The metabolism of benzoic acid has been examined in the horse, using 14C- and deuterium-labelled compounds. Chromatographic analysis of the urine showed the presence of hippuric acid, benzoyl glucuronide and benzoic acid and a discrete band which accounted for 2% of the dose administered. This material was isolated by solvent extraction and HPLC and, following treatment with diazomethane, examined by GC/MS. The major component of this fraction was 3-hydroxy-3-phenylpropionic acid methyl ester, which was accompanied by very much smaller amounts of cinnamic acid methyl ester and acetophenone. The two latter minor components have been shown to be artefacts produced during workup and analysis. Cinnamic acid methyl ester arises by the thermal decomposition of 3-hydroxy-3-phenylpropionic acid methyl ester on the GC column. It is proposed that acetophenone has formed, during workup, by decarboxylation of 3-keto-3-phenylpropionic acid. It is suggested that 3-hydroxy and 3-keto-3-phenylpropionic acids, which are also endogenous in horse urine, have arisen by an addition of a 2 carbon fragment to benzoyl CoA, in a sequence analogous to the reactions of fatty acid biosynthesis. Some implications of the metabolic interrelationships between xenobiotic acids and fatty acids are discussed.

Animals↗

Time budgets of older people:" a window on four lifestyles.

The purposes of this research were first to describe how a group of urban elderly spend their days and, second, to examine the responsiveness of the behavioral day to rather marked environmental and personal differences. Detailed time budgets for one full day (including the content, duration, social and environmental context, and the amount of liking for each activity) were obtained from 535 persons, from four groups: independent community residents, public housing tenants, recipients of intensive in-home services, and an institutional waiting list group. Consistent patterns appeared across groups, particularly in the amount of time spent in the various social contexts and in most discretionary activities. However, the independent groups spent more time than the service groups away from home and in obligatory tasks such as housework, cooking, and shopping. Independent groups tended to express greater liking for many activities but not for more novel activities which the service groups liked equally as well.

Aged↗

Plasma concentrations and urinary excretion of nandrolone and/or its metabolites after intramuscular injection of nandrolone phenylpropionate to horses.

A radioimmunological method was used as a screening procedure to determine the period of detection or "clearance time", for the horse, of therapeutic doses of the synthetic anabolic steroid nandrolone phenylpropionate. Seven horses, either at rest or being exercised, were given a course of weekly intramuscular injections of the steroid. On the separate occasion, some of the horses were given a single intramuscular injection of the same compound. The weekly injections maintained a high plasma concentration of nandrolone and/or metabolites. The mean (+/- sd) period of detection in plasma of these compounds was 23 (+/- 2) days (range 21 to 25) in resting horses and 20 (+/- 6) days (range 14 to 27) in exercised animals. The mean period of detection in urine was 25 (+/- 7) days (range 16 to 32) and 25 (+/- 12) days (range 9 to 38) for resting and exercised horses, respectively. After a single intramuscular injection to resting horses, the mean periods of detection were 12(+/- 2) days (range 9 to 15) and 13 (+/- 2) days (range 11 to 16) in plasma and urine, respectively. In all experiments there was considerable individual variation in the time taken for the plasma and urine concentrations to return to pre-dose values. This variation was particularly marked in the urine of exercised horses given a course of injections. With horses in training, this period may be over 5 weeks, a period approaching the minimum of 42 days advocated by the Royal College of Veterinary Surgeons that the therapeutic use of anabolic steroids should be discontinued before racing.

Anabolic Agents↗

Enkephalin-immunoreactive perikarya in the cat raphe dorsalis.

The serotonin-containing nucleus raphe dorsalis (RD) of the cat contains numerous leucine-enkephalin immunoreactive cells, throughout its rostral-caudal extent. The distribution of the enkephalin neurons closely parallels the cytoarchitectural boundaries of the RD, as described in previous Nissl preparations. Enkephalin perikarya are most numerous along the midline of the RD, but also extend ventrally, into the dorsal portion of the nucleus centralis superior, and laterally, into the 'wings' of the rostral RD, at the level of the IV nucleus. The possible contribution of these enkephalin cells to endogenous pain control systems is discussed.

Animals↗

Metabolic conjugation of some carboxylic acids in the horse.

1. 14C-Labelled benzoic acid, salicylic acid and 2-naphthylacetic acid were administered orally to horses, and urinary metabolites investigated by chromatographic and mass spectral techniques. 2. [14C]Benzoic acid (5 mg/kg) was eliminated rapidly in the urine, and quantitatively recovered in 24 h. The major urinary metabolite was hippuric acid (95% of dose) with much smaller amounts of benzoic acid, benzoyl glucuronide and 3-hydroxy-3-phenylpropionic acid. Administration of [ring-D5]benzoic acid together with [14C]benzoic acid to a pony permitted the mass spectral determination of metabolites of the exogenous benzoic acid metabolites in the presence of the same endogenous compounds. 3. [14C]Salicylic acid (35 mg/kg) was eliminated rapidly in the urine, 98% of the 14C dose being excreted in 24 h. The major excretion product was unchanged salicylate (94% of dose). Gentisic acid, salicyluric acid and the ester and ether glucuronides of salicylic acid were very minor metabolites. 4. 2-Naphthyl[14C]acetic acid (2 mg/kg) was excreted very slowly in the urine, with 53 and 77% of the 14C dose being recovered in six days. 2-Naphthylacetylglycine was the major metabolite (26 and 38% dose) and in addition, the glucuronic acid and taurine conjugates were excreted together with unchanged 2-naphthylacetic acid. 5. The study has shown that the horse can utilize glycine, taurine and glucuronic acid for conjugation of xenobiotic carboxylic acids, and that the relative extents of these pathways are governed by the structure of the carboxylic acid.

Animals↗

The disposition and metabolism of the synthetic prostaglandin fluprostenol (ICI 81,008) in the horse.

1. Following single intramuscular doses of [14C]fluprostenol (0.5--2.4 micrograms/kg) to three female horses and to three gelded male horses, radioactivity was present in the plasma within 5 min; peak concn. (0.32--1.30 ng/ml fluprostenol equiv.) occurred 5 to 90 min after injection. Radioactivity was still present in the plasma of the females after three days. About 88% of fluprostenol is bound to plasma proteins. 2. Radioactivity was present in the parotid saliva of the gelded male horses within 10 min. Peak concn. (45--91 pg/ml fluprostenol equiv.) occurred from 5 min to 1 h after injection. Saliva : plasma concn. ratios varied inversely with saliva flow rate and limiting ratios were 0.33 and 0.41 for the combined results of two experiments on each of two male horses; the calculated value is 0.46 Chromatography indicated that the majority of plasma and saliva radioactivity was [14C]fluprostenol. 3. Excretion of radioactivity in the urine was rapid and virtually complete 12 h after dosing. The total radioactivity excreted in urine by the female horses was 45% of the dose (96 h) and by the gelded male horses 53% (30 h). About 30% of the radioactivity present in the urines was unchanged fluprostenol. 4. Faecal excretion, which was substantially complete after 2 days, accounted for 32% of the radioactivity administered to the female horses. 5. Tissue conc. of radioactivity in the female horses at four days were below the limits of detection (90 pg/g), but 0.2--0.9% of the dose was detected at the site of injection.

Animals↗

A gas chromatographic screening procedure for the detection of non-steroidal anti-inflammatory drugs in horse urine.

A gas chromatographic screening procedure for the non-steroidal anti-inflammatory group of drugs is described. The method invovles on-column methylation of the carboxylic acid group using trimethylanilinium hydroxide as the methylating reagent. Fifteen such drugs were studied. Eight of these were detected in urine collected from horses that had received these compounds orally and for these drugs, rates of urinary excretion are recorded. Seven other members of this group of drugs were shown to be detectable by this procedure but in these cases the drug was added to urine and not administered to the horse.

Animals↗

Studies related to the metabolism of anabolic steroids in the horse: a gas chromatographic mass spectrometric method to confirm the administration of 19-nortestosterone or its esters to horses.

A method is described to confirm the presence of 19-nortestosterone metabolites in urine after the administration of veterinary preparations of this anabolic steroid to horses. The method is based upon the detection, by gas chromatography mass spectrometry or selected ion monitoring, of an isomer of estrane-3,17-diol in the urine.

Animals↗