Attitudes of veterinarians toward emerging competencies for health care practitioners.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
E A Stone
Publications and source records attributed to E A Stone.
Stress-induced increase of extracellular levels of cyclic AMP in rat cortex.
Previous studies have suggested that stress may increase levels of cyclic AMP (cAMP) in the brain but these findings have been controversial due to the use of stressful procedures to inactivate brain enzymes. The present experiment therefore used a non-stressful technique, microdialysis, to assay extracellular levels of cAMP in the rat cortex after stress. Experiments were conducted 2 days after implantation of probes in the frontal cortex. Significant increases were found after the mild stressors of restraint or intraperitoneal injection of saline suggesting that increased tissue levels of cAMP had occurred. These responses were potentiated by local infusion of the phosphodiesterase (PDE) inhibitor, rolipram. It is concluded that one or more adenylate cyclase-coupled receptors in the cortex is activated by mild stress and that this activation can be detected in vivo by microdialysis.
Adenylyl Cyclases↗
Immunohistochemical studies of noradrenergic-induced expression of c-fos in the rat CNS.
Previous studies have shown that stimulation of adrenergic receptors in the rat brain causes increased levels of mRNA of the immediate early gene, c-fos. The present studies were undertaken to determine if this stimulation also induces increased levels of c-fos immunoreactivity in the central nervous system (CNS). Rats were treated with the alpha-2 adrenoceptor blockers, yohimbine or atipamezole, or with restraint stress to activate central noradrenergic activity and were perfused 2 h later for immunohistochemical analysis of the cerebral cortex. Yohimbine, atipamezole and restraint stress each was found to cause increases in c-fos-like immunoreactivity (c-fos-li). Western blot analysis revealed increased c-fos protein in the cortex after yohimbine treatment. The c-fos-li response to yohimbine was blocked by prior administration of the beta receptor antagonist, dl-propranolol, and to a lesser degree by the alpha-1 antagonist, prazosin. It is concluded that adrenergic receptor stimulation in the cortex causes increased production of c-fos or fos related antigens and that this (these) immediate early gene product(s) may play a role in noradrenergic function in the CNS.
Adrenergic alpha-Antagonists↗
Noradrenergic-induced expression of c-fos in rat cortex: neuronal localization.
beta Adrenoceptors in the rat forebrain have been shown to exist predominantly on astrocytes. Studies were undertaken to determine whether the cellular localization of c-fos expression caused by the activation of brain beta receptors would have a similar cellular localization. Double label light and electron microscopic immunohistochemical experiments with a glial (glial fibrillary acidic protein, GFAP) and neuronal marker (neurofilament protein, NFP) were undertaken in rats treated with the adrenergic drug, yohimbine. These studies revealed a predominantly neuronal localization of Fos protein in the cerebral cortex. The latter results indicate that neurons are the postsynaptic noradrenergic target cells in which this immediate early gene is expressed in response to the stimulation of beta adrenoceptors. The possible relation of these findings to the glial localization of these receptors is discussed.
Animals↗
Cellular localization of responses to catecholamines in brain tissue.
Explore the source record for details and available documents.
Brain↗
Effects of freezing on mechanical properties of rat skin.
Two test specimens of skin were cut from the lateral aspect of each hind limb of 9 rats. Specimens were contiguous, thereby providing matched pairs. One specimen was immediately placed in liquid nitrogen for 5 minutes, then stored at -70 C and tested within 3 to 4 weeks. Within 5 minutes of harvest, the second specimen was used for immediate material testing. Basic engineering material tests were used to measure strength, loading response, and elastic and viscous properties. Each matched pair of tissues was used for the same procedure. Quasistatic uniaxial tensile tests were used to apply deformations to the test specimens, and resulting loads were recorded. Stress and strain were calculated from the recorded data, providing information on yield strength, ultimate strength, fracture strength, and loading response. Each matched pair of specimens represented 1 repetition; 6 repetitions were made of each observation. Statistical analysis indicated that tissue freezing significantly (P less than 0.05) increased fracture strength, but did not affect strength, ultimate strength, or loading response. Dynamic vibration response tests were used to find mechanical mobility of the specimens, thereby providing information on elastic and viscous behaviors, which were quantified by calculation of spring and damping coefficients, respectively. As before, 6 repetitions were used. Statistical analysis indicated that tissue freezing did not affect these coefficients.
Animals↗
c-Fos response to administration of catecholamines into brain by microdialysis.
The present studies investigated the use of microdialysis for the infusion of catecholamines into the brain in studies of immediate early gene (IEG) activation. c-Fos like immunoreactivity was examined histochemically in cortical tissue surrounding a dialysis probe implanted in the medial prefrontal cortex. No c-fos reactivity was observed at 48 h post implantation in control animals not probe-infused or infused 2 h earlier with Ringer's buffer. Marked reactivity was found in animals infused with a solution of norepinephrine (NE). The latter was blocked by coinfusion of the beta adrenoceptor antagonist, timolol. It is concluded that direct infusion of NE by dialysis can induce c-fos expression in cells of the cerebral cortex and that this effect is primarily via beta-adrenoceptors. Microdialysis therefore represents a useful technique in studies of IEG responses to brain catecholamines.
Animals↗
Sinus mucocele secondary to craniofacial trauma in a dog.
A sinsus mucocele formed in the frontal sinus of a dog secondary to obstruction of the nasofrontal opening. The dog was successfully treated by surgical enlargement of the nasofrontal opening, curettage of the sinus epithelium, and placement of a fat graft and drain in the sinus. Although mucocele formation is uncommon in animals, it should be considered as a differential diagnosis for masses of the sinonasal area. Characteristic radiographic and cytologic findings should alert the clinician to this diagnosis, and along with aggressive treatment, should shorten the diagnostic and treatment delay experienced by the dog in this report.
Animals↗
Further evidence for a glial localization of rat cortical beta-adrenoceptors: studies of in vivo cyclic AMP responses to catecholamines.
The present experiments were designed to clarify the cellular localization of postsynaptic beta-receptors in the rat cortex by studying the cellular source and pharmacological characteristics of in vivo cAMP responses to catecholamines. The method used to study in vivo cAMP responses in the brain involved microdialysis both to deliver catecholamines to cerebral tissue and to sample cAMP released in response to local beta-receptor activation. It was found that selective blockade of the metabolism of glial cells by fluorocitrate infusion produced a virtually complete (90%) inhibition of the cortical cAMP response to norepinephrine (NE). Selective damage of neurons by kainic acid infusion had little effect on the response. Pharmacological experiments showed that the response was selectively antagonized by a beta 1-receptor blocker which also selectively antagonized the cAMP response to NE in brain slices known to be localized in glial cells. These results support the hypothesis that beta-adrenoceptors of the rat cortex are predominantly localized on glial cells and therefore strongly suggest that these cells are an important target of the locus coeruleus noradrenergic system.
Analysis of Variance↗
Noradrenergic activation of immediate early genes in rat cerebral cortex.
Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.
Animals↗
Glial localization of adenylate-cyclase-coupled beta-adrenoceptors in rat forebrain slices.
Fluorocitrate (FC), a selective inhibitor of glial cell respiration, was used to estimate the extent to which glial cells contain adenylate cyclase-coupled beta-adrenoceptors in rat brain slices. The drug blocked 75-95% of the elevation of cyclic AMP caused by the beta-agonist, isoproterenol, in the 4 forebrain regions sampled (frontal and parietal cortex, caudate nucleus, olfactory tubercle). Intracellular recording of neurons in the treated slices confirmed that they were unaffected by FC. Treatment with the neurotoxin, kainic acid, eliminated all electrophysiological activity but did not affect the cAMP response. The results indicate that glial cells contain the preponderance of adenylate-cyclase-coupled beta-adrenoceptors in slices of the rat forebrain and may constitute an important target of the central noradrenergic system in vivo.
Adenosine Triphosphate↗
Surgically induced tumor seeding in eight dogs and two cats.
Surgically induced tumor seeding was diagnosed in 8 dogs and 2 cats. All animals had histologic confirmation of neoplasia in an unusual location or pattern, and a history of surgical manipulation of a similar histologic-type tumor at the site of seeding. Highly malignant carcinomas (8/10 animals) were the most common tumor type. Seeding occurred secondary to a variety of surgical procedures and in the face of various adjuvant therapies. Seeded tumors were recognized from 2 to 30 weeks after the causal procedure (median, 6 weeks). Survival times after the causal procedure ranged from 15 to 131 weeks (median, 45 weeks) and 8 of 10 animals died or were euthanatized because of seeded tumors.
Animals↗
In vivo measurement of extracellular cyclic AMP in the brain: use in studies of beta-adrenoceptor function in nonanesthetized rats.
Microdialysis measurement of extracellular cyclic AMP (cAMP) in the cerebral cortex of conscious rats was evaluated as a method for assessing central beta-adrenoceptor function in vivo. Extracellular levels of the nucleotide were found to average 3 pmol/ml under baseline conditions. Local infusion of the beta-agonists norepinephrine (NE) and isoproterenol produced rapid (3 min) and marked (three- to sevenfold) dose-dependent increases in extracellular cAMP, which were potentiated by the phosphodiesterase inhibitor rolipram, and blocked by the beta-antagonist timolol. Responses to both catecholamines underwent rapid desensitization (6-9 min) and recovered within several hours. Time-course studies revealed that the baseline cAMP level underwent a gradual increase and then a decrease over the course of a single 8-h run, and peaked at 24 h postimplantation. Responses to NE were stable for the first 24 h after implantation, then increased at 48 and 120 h. The causes of the latter changes may include reactions to novelty, local inflammatory responses, and/or reactions of adjacent glial cells to implantation. Overall, the results indicate that the microdialysis-cAMP method can be extended to nonanesthetized animals and may be a useful tool for studying neurotransmission at central adenylate cyclase-coupled membrane receptors during various behavioral states.
Anesthesia↗
Catecholamine-induced desensitization of brain beta adrenoceptors in vivo and reversal by corticosterone.
The function of beta adrenoceptors in the brain was studied with a new technique involving the microdialysis collection of extracellular cyclic AMP (cAMP). Prolonged infusion of isoproterenol (2 hr) was found to induce a marked desensitization of the beta receptor-cAMP response. Administration of corticosterone (10 mg/kg) 3 hrs prior to the infusion markedly attenuated the desensitization. The results indicate that the catecholamine-induced densensitization of brain beta adrenoceptors can be studied in vivo and that corticosterone is capable of reversing this effect in the brain as has been reported previously for peripheral tissues.
Animals↗
Use of microdialysis to measure brain noradrenergic receptor function in vivo.
The present studies were undertaken to explore the use of intracerebral microdialysis to measure brain adrenergic receptor activity in vivo using the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid as an index of receptor function. An initial study with brain slices showed that extracellular levels of cAMP were highly correlated with intracellular levels after noradrenergic receptor activation. Detectable levels of extracellular cAMP were obtained from microdialysis probes implanted in the frontal cortex. Stable levels (3.5 +/- 2.7 pmol/ml) were obtained between 1.5 and 7 h after implantation. Perfusion of probes with NE (10(-5) to 10(-3) M) led to dose-dependent increases in cAMP efflux. The response to NE was blocked by infusion of the beta-antagonist, timolol, indicating that it reflected beta-receptor activation. Similar responses were obtained at 2 and 24 h after implantation indicating that the responses were not affected by acute traumatic effects of implantation. The findings show that the microdialysis technique can be successfully applied to the in vivo study of central adrenoceptor function. This suggests that the in vivo measurement of second messengers by microdialysis will provide a valuable new neurochemical and neuropharmacological technique.
Animals↗
Renal dysfunction in dogs with pyometra.
Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included CBC; serum biochemical evaluation; urinalysis; urine and uterine bacteriologic culture; uterine morphologic features; and light, electron, and immunofluorescent microscopic evaluation of renal tissues. Measurements of 24-hour creatinine clearance, protein excretion, Na excretion, and urine volume were made in 12 dogs without azotemia. Of 27 dogs, 26% were azotemic and 89% had a urine sp gr less than 1.035. Glomerular filtration rate was reduced in 75% of 12 dogs without azotemia. None of these 12 dogs was proteinuric. Examination of renal biopsy specimens revealed a high prevalence of mild tubulointerstitial nephritis, but few specific glomerular lesions. Minimal immunofluorescence was detected within the mesangium in 18% of the dogs. Immunofluorescence was not associated with the interstitium or tubules. Urinary tract infection was detected in 22% of the dogs. Escherichia coli and Klebsiella were recovered from the uterus in 59 and 15% of the dogs, respectively. Low urine specific gravity values were obtained from dogs without azotemia and from dogs with uterine cultures considered negative for E coli and other gram-negative bacteria. The reduction in glomerular filtration rate was a functional abnormality not correlated with structural damage in the glomerulus.
Animals↗
Architecture and structure of canine veins with special reference to confluences.
The occurrence of cell-infiltrated intimal lesions at the confluence of many small tributaries with canine jugular and femoral veins suggested that these areas (confluences) might 1) differ structurally from the rest of the receiving vein and 2) serve as initiation sites for thrombi. To explore these possibilities, the number of tributaries was determined by careful blunt dissection, and the architecture of confluences was studied by light and scanning and transmission electron microscopy. In addition to confluences formed by a named tributary (omobrachial), canine jugular veins averaged 11 confluences formed with small (0.2 to 2.5 mm diameter) unnamed tributaries that had not been previously described. Femoral veins averaged eight confluences of which four were formed with small unnamed tributaries. Double-leafed valves were found at 90% of jugular and 76% of femoral vein confluences. Previously such valves were described only at the confluence of superficial with deep leg veins. Corrosion casts of iliac, saphenous, azygous, costocervical, and maxillary veins as well as cranial and caudal vena cava demonstrated a similar pattern of tributaries and valves. The three structures (receiving vein, tributary, valves) that formed the confluence differed, necessitating considerable modification as they approached the area of fusion. Jugular and femoral vein walls contained 5 to 10 layers of smooth muscle, abundant collagen, and a small amount of elastin. Tributary walls contained 0 to 2 discontinuous smooth muscle cell layers, limited collagen, and no elastin. As receiving veins approached a confluence, the thickness decreased by 15 to 77% except at valve attachment sites, which were thickened. A cluster of smooth muscle cells formed the junction of valve leaflets with vein. Endothelium was continuous over the luminal surface of all three structures. Calculations showed that these small-valved tributaries make only a small contribution to venous return. On the other hand, there is considerable information to support the concept that local attenuation of the vein wall would lead to localized vessel dilation, resulting in rupture of the endothelium and basement membrane.
Animals↗
Novel effect of chronic corticosterone treatment on escape behavior in rats.
Chronic administration of corticosterone in rats (4-35 mg/kg/day) produces a marked dose-dependent increase in the frequency of escape behavior observed when animals are held by the tail on a flat surface. The effect is fully developed after 3 days treatment. It is not the result of an increase in spontaneous motor activity since the hormone tends to reduce the latter behavior. Adrenalectomy decreases the escape behavior and tends to do so to a greater degree in rats subjected to chronic stress (restraint) than in nonstressed controls. The results suggest that endogenous corticosterone serves to maintain the above escape behavior during chronic stress.
Administration, Oral↗