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Biomedical subjects

R Farrell

Publications and source records attributed to R Farrell.

At least 19 recordsLinked to original sources

Environmental enrichment enhances recovery of function but exacerbates ischemic cell death.

Prior exposure to brief 'conditioning' episodes of ischemia protects hippocampal CA1 neurons against a subsequent more severe ischemic insult. However, protected cells exhibit abnormal function and as survival times are extended this ischemic tolerance dissipates and cells begin to die. In this study, we sought to determine whether environmental enrichment could alter the above pattern of delayed cell death and functional impairment in a gerbil model of ischemic tolerance. Gerbils received either ischemic preconditioning, 5 min of ischemia without preconditioning or sham surgery. Three days after ischemia, gerbils were placed in either an enriched environment or standard laboratory housing. Open field habituation was assessed 3, 7, 10, 30 and 60 days after ischemia. Subsequently, animals were trained in two versions (win-shift and win-stay) of a T-maze task. Following behavioral testing, extracellular CA1 field potential amplitudes and CA1 cell counts were determined. Initial open field activity was significantly higher in all experimental groups compared to sham animals (P<0.001). By 60 days, enriched ischemic preconditioned and enriched ischemic gerbils were not different than shams whereas non-enriched, ischemic preconditioned and ischemic gerbils continued to have higher activity scores (P<0.05). Preconditioned and enriched ischemic animals learned the win-shift T-maze problem as quickly as shams while non-enriched ischemic gerbils were severely impaired compared with all other groups (P<0.001). Only the sham and enriched preconditioned groups readily acquired the win-stay paradigm. CA1 field potential amplitudes were lower (P<0.05) in ischemic than sham gerbils irrespective of treatment. Surprisingly, CA1 cell counts were significantly lower (P<0.01) in enriched versus non-enriched ischemic preconditioned animals. These data demonstrate that early, intensive intervention after ischemia can improve functional outcome but that this is accompanied by increased brain damage. Careful consideration needs to be given to the timing of rehabilitation after stroke and related types of brain injury.

Animals↗

Synthesis and antispasmodic activity of analogues of natural pterosins.

The synthesis of an extensive range of analogues of natural pterosins using modified Heck coupling is reported. The smooth muscle relaxant activity of these compounds has been examimed. Several compounds with significant smooth muscle relaxant activity have been identified.

Journal Article↗

Smooth muscle relaxant activity of pterosin Z and related compounds.

The natural products pterosin Z, acetylpterosin Z, originally from the fern Pteridium aquilinum, and their isopterosin analogues have been synthesized and their smooth muscle relaxation activity has been measured. All of the test compounds show activity with pterosin Z being the most active (EC50 = 1.3 +/- 0.1 x 10(-6) M), exhibiting 100 times the activity reported for the related fern metabolites onitin (EC50 = 1 x 10(-4) M), onotisin (EC50 = 2 x 10(-3) M) and otninoside (EC50 = 7 x 10(-4) M). The smooth muscle relaxant activity of pterosin Z is approximately equipotent with that of the related fungal pterosin (EC50 of 2.9 +/- 1.6 x 10(-6) M). These results suggest that smooth muscle relaxant activity is reduced when a phenol group is present in the pterosin nucleus and when one of the dimethyl groups is derivatized.

Animals↗

Claudication on mastication following bilateral external carotid artery ligation for posterior epistaxis.

This case highlights a potentially disabling complication of intermittent claudication in the region of the masseter muscles on mastication, following bilateral external carotid artery ligation for epistaxis. Although there have been few reports of this complication this may be a reflection of the fact that the operation is rarely performed, and not because the complication is rare. Its potentially disabling nature, and its possible common occurrence after this procedure make awareness of it by surgeons who may carry out this procedure important.

Carotid Artery, External↗

The clinical role of shoulder ultrasound.

BACKGROUND: Rotator cuff surgery is facilitated by accurate pre-operative information regarding the presence and size of cuff tears, and the extent of any cuff retraction or lamination. METHODS: A total of 117 consecutive patients who underwent shoulder ultrasound followed by surgical management were assessed, and the pre-operative ultrasound diagnoses were correlated with the operative findings. RESULTS: Ultrasound was found to be reliable for the detection of full-thickness cuff tears (positive predictive value 96%). In the assessment of partial thickness tears, ultrasound produced few false positives, but failed to diagnose a significant proportion of these lesions. Lamination and other interstitial cuff pathology were not reliably detected by ultrasound. In the diagnosis of subacromial impingement, ultrasound produced few false positives (positive predictive value 95%), but did produce a significant number of false negative results (negative predictive value 66%). CONCLUSIONS: Ultrasound is cheaper than MRI and arthrography, and is both non-invasive and 'dynamic'. It is reliable in the diagnosis of full-thickness cuff tears and is a useful adjunct in the diagnosis of cuff impingement and partial thickness tears, but is very much operator-dependent.

Adolescent↗

Levels of superoxide dismutase mRNA in rat lens: effect of aging.

Superoxide dismutase, the enzyme catalyzing the dismutation of O2.- to H2O2 is known to be present in various ocular and nonocular tissues. In this communication we have determined the gene expression of this enzyme in rat lenses. The investigations have been conducted as a function of age using RNase protection assay. These in vitro assays for the corresponding mRNA suggested that the transcription of the gene is age variant, increasing as a function of age. The levels were significantly lower in the young lenses in comparison to the older lenses.

Aging↗

Protocols for college health nurses: alive and well in the 1990s.

This article seeks to assist college health nurses in developing appropriate protocols for patient care. In addition, the authors outline factors influencing protocol content, design, and development and describe steps in creating individualized protocols by practice setting. To provide college health nurses with a basic understanding of protocols, the authors offer definitions and examples of appropriate and inappropriate use, and show how protocols can influence the delivery of patient care. Although protocols may provide college health nurses with directives for managing specific health problems, they require a sophisticated level of judgment and skill in their implementation.

Female↗

Heparin and dihydroergotamine prophylaxis against thrombo-embolism after hip arthroplasty.

A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy.

Aged↗

Free radicals appear to affect survival of hepatocytes at 4 degrees C.

1) Rat hepatocytes, stored in a simple salts medium for 24 h at 4 degrees C, retain more than 80% of their capacity to synthesize glucose from lactate. 2) The combination of NH4Cl with oleate is cytotoxic during storage and during subsequent incubation of hepatocytes from 48 h starved rats, but not to hepatocytes from fed rats. 3) Protection against cytotoxicity is afforded by albumin and by a number of other compounds, notably polyols and glycerol. 4) These compounds appear to exert their effects by scavenging free radicals and, in the case of polyols and glycerol, by supplying reducing equivalents to maintain the redox state of the cell in the face of increased flux through glutathione peroxidase.

Ammonium Chloride↗

Measurement of steady state protein degradation in cultured human muscle cells.

Double label techniques for measurement of protein turnover in cultured cells are described. In the isotope withdrawal method protein in cultured muscle is labeled with two isotopes of the same amino acid for 24 to 100 h, followed by exposure to fresh medium containing one isotope only at the same specific activity for an additional 24 to 48 h. In the isotope addition method the order of addition of single and double-labeled media is reversed. After incubation the ratio of the two isotopes in the cell protein is a function of the incubation time and the degradation rate constant KD; KD can readily be calculated using a graphical or iterative method. In mixed cultures of human muscle with initial incubation ranging 24 to 159 h, the KD's obtained from various incubation times were similar. Both the isotope withdrawal and the isotope addition methods gave a KD value of 0.018 h-1 similar to values obtained by two different single isotope methods which monitor the appearance of free isotope in the medium of previously labeled cells. There were no differences of KD values obtained in cultures of muscle from normal patients and those with denervation, inflammatory myopathies, or nonspecific myopathic biopsy changes. When proteins were separated by gel electrophoresis, those of molecular weight greater than 60,000 had higher average KD values as compared to lower molecular weight proteins. The double isotope labeling method has the advantage of being easily applied to cultures with small numbers of cells and is potentially useful in obtaining the degradation rates of individual cellular proteins. The major disadvantages are (1) in their present form the methods can be used only in steady state cultures and (2) they require rather long (24 h) labeling times.

Cells, Cultured↗

Effect of starvation and refeeding on polyamine concentrations and ornithine decarboxylase antizyme in mammary gland of lactating rats.

Starvation caused a marked increase in putrescine content in mammary gland of lactating rats, together with a marked decrease in activity of ornithine decarboxylase and appearance of measurable ornithine decarboxylase antizyme. 2. Refeeding for 5 h caused disappearance of free antizyme and ornithine decarboxylase activity returned to the value in fed animals. Putrescine concentration remained elevated. 3. There was no significant change in nucleic acid content of mammary gland from starved rats, but spermidine and spermine contents increased significantly. 4. Refeeding for 5 h returned the spermidine content of mammary glands to 'fed' values, and significantly decreased the content of spermine, although it did not reach control values. Thus changes in polyamine content of mammary gland in starved rats are clearly dissociated from changes in either RNA content or activities of polyamine-synthetic decarboxylases. 5. Starvation caused a fall in the content of spermidine in liver, with no change in spermine content. Refeeding for 5 h returned the spermidine content to 'fed' values.

Animals↗

Effects of inhibition of protein synthesis by cycloheximide on lipogenesis in mammary gland and liver of lactating rats.

1. Administration of cycloheximide (an inhibitor of protein synthesis) to lactating rats raised the concentrations of amino acids, and in particular, the branched-chain amino acids (valine, leucine and isoleucine) in blood, liver and mammary gland. 2. Inhibition of protein synthesis increased the incorporation in vivo of L-[U-14C]leucine into lipids of mammary gland and liver. 3. Cycloheximide treatment caused no immediate change in the overall rate of lipogenesis in vivo (measured with 3H2O) in mammary gland but increased the rate in liver 3-fold; this latter effect also occurred in livers of virgin rats. 4. The increased rate of hepatic lipogenesis was not accompanied by significant changes in the plasma insulin concentration or the activity of acetyl-CoA carboxylase. 5. Although cycloheximide decreased the entry of total triacylglycerol into the circulation it did not alter the rate of secretion of newly synthesized saponifiable lipid. 6. Cycloheximide slightly stimulated lipogenesis from endogenous substrates in isolated hepatocytes, but this effect was abolished when lactate was the exogenous substrate. 7. Administration of cycloheximide to virgin rats decreased liver glycogen and increased the hepatic content of glucose 6-phosphate, pyruvate and lactate. 8. It is concluded that (a) there is no short-term link between the rate of protein synthesis and lipogenesis in the lactating mammary gland and (b) the increased rate of hepatic lipogenesis in cycloheximide-treated rats is mainly due to stimulation of glycogenolysis, glycolytic flux and consequent increased availability of pyruvate.

Animals↗

Brain site variations in effects of morphine on electrical self-stimulation.

Pairs of bipolar electrodes were stereotaxically aimed at two of three sites: the locus coeruleus (LC), the substantia nigra, pars compacta (SNC), and the median forebrain bundle (MFB). Rats were shaped to bar-press for trains of intracranial electrical stimulation presented as pairs of monophasic pulses. The first pulse of a pair (the C, conditioning pulse) was followed by a second pulse (the T, test pulse) after a parametrically varied interval. The effects of chronic morphine administration were tested in a paradigm of 7 days saline, 7 days morphine, 1 day morphine+naloxone, and 6 days post-drug saline. High doses of morphine (5 mg/kg) depressed response rates for intracranial self-stimulation (ICSS). LC placements and those just lateral or ventral to the LC showed large increases in ICSS rates under morphine (2.5 mg/kg). This area was delimited on either side by tips that showed response rate depressions under morphine. MFB placements yielded response rate facilitations under morphine. Sites medial to the MFB and ventral within the MFB showed rate depressions under morphine. Dorsal substantia nigra placements showed facilitated rates, whereas placements ventral within the SNC and substantia nigra, pars reticulata (SNR) produced more variable results, with rates tending to be depressed by morphine. The ICSS procedure may be a useful animal model for detecting the abuse potential of drugs.

Animals↗