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Biomedical subjects

R T Robertson

Publications and source records attributed to R T Robertson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Diflunisal-induced maternal anemia as a cause of teratogenicity in rabbits.

Diflunisal [5-(2,4-difluorophenyl)-salicylic acid] is a new analgesic antiinflammatory drug that, when administered orally to rabbits at 40 and 60 mg/kg/day, caused terata, most commonly axial skeletal defects. These same dosage levels also caused a severe maternal hemolytic anemia following a dramatic decrease in erythrocyte ATP levels. The teratogenicity, anemia, and depletion of ATP were unique to the rabbit among species examined. To test the possible causality between the teratogenic effects and anemia induced by diflunisal, a single dose of 180 mg/kg diflunisal was administered to rabbits on gestation day 5. This treatment produced an anemia that persisted through gestation day 15 in addition to causing the characteristic axial skeletal defects. Since diflunisal was cleared from maternal blood before gestation day 9, the critical day for induction of similar axial skeletal defects by hypoxia, the skeletal malformations probably resulted from maternal hypoxia secondary to anemia and not from a direct and specific effect of the drug on the embryo. In addition, we observed that the diflunisal level in the embryo was less than 5% of the peak maternal blood level probably as a result of high plasma protein binding of diflunisal in the maternal blood (greater than 98%). This relatively low placental transfer may explain the lack of diflunisal teratogenicity in rats and mice compared to aspirin which crosses the placenta more readily. These studies demonstrate that a species that exhibits unusually severe drug-specific maternotoxicity is probably an unsuitable model for the prediction of the teratogenic potential of that drug in humans.

Abnormalities, Drug-Induced↗
PubMed1984

Regional effect of monosodium-L-glutamate on the superficial layers of superior colliculus in rat.

Systemic administration of monosodium-l-glutamate by single injections of 4 mg/g body weight in infant rats (2-10 days of age) results in acute swelling of cytoplasm and nuclear pyknosis of neurons in the stratum zonale and stratum griseum superficiale of the superior colliculus. Multiple daily doses of 4 mg/g body weight monosodium-l-glutamate result in an almost complete loss of neurons in these two superficial layers. The deeper layers appear not to be affected. No pathological effects were observed in the lateral geniculate body or pretectal complex. Light- and electron-microscopic studies reveal that the optic nerves are remarkably shrunken and many myelinated as well as unmyelinated axons are lost. Injection of 3H-proline into the vitreous body of one eye results in limited transport to the suprachiasmatic nucleus, lateral geniculate body and to lateral portions of the superior colliculus. The small percentage of intact axons in the optic nerve, as well as the limited proline transport from the eye, suggest that administration of monosodium-l-glutamate leaves intact some optic fibers, a portion of which belongs to the retinohypothalamic tract.

Animals↗
PubMed1984

Two inhibitors of angiotensin-converting enzyme, enalapril and captopril, increase salt appetite of rats.

Male rats were orally administered an inhibitor of angiotensin-converting enzyme (ACE), N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-1-ala-1-pro maleate (enalapril, MK-0421) at dosage levels of 10, 30, and 90 mg/kg X d. After 2-6 wk of dosing, the rats receiving 30 and 90 mg/kg X d produced large numbers of seminal plugs and had lacerated penises due to licking in an attempt to recover urine. Providing 0.9% saline as the source of drinking water prevented this behavior and subsequent lesions. There were no adverse effects on reproductive performance. A subsequent study showed that enalapril at 5 mg/kg X d po and captopril (another ACE inhibitor) at 25 mg/kg X d po increased NaCl intake in rats. Our results with captopril confirm those of Fregly (1980) and Evered and Robinson (1983) and show that both converting-enzyme inhibitors (enalapril and captopril) increase salt appetite in rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Organization of projections from the superior colliculus to the thalamic lateral posterior nucleus in the rat.

Injections of horseradish peroxidase into the lateral posterior nucleus (LP) of the rat thalamus resulted in retrograde labeling of neurons in the superior colliculus (SC). Approximately 80% of the labeled cells occurred in the stratum opticum and 20% in the stratum griseum superficiale. The system of projections is organized such that medial parts of SC project to dorsal LP and lateral parts of SC project to ventral LP.

Animals↗
PubMed1983

Mevalonate supplementation in pregnant rats suppresses the teratogenicity of mevinolinic acid, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase.

Mevinolin is a fungal metabolite, and in the hydroxyacid form, mevinolinic acid, it is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-Co A) reductase, an enzyme essential in cholesterol biosynthesis. Oral administration of 800 mg/kg/day of mevinolin to rats from days 6 through 17 of gestation produced fetal malformations of the vertebrae and ribs in 29% of the litters, and there was a treatment-related increase in the incidence of gastroschisis. Mevinolinic acid at 60 and 90 mg/kg/day also produced fetal malformations of the vertebrae and ribs, and these teratogenic manifestations were markedly suppressed by coadministration of the product of HMG-Co A reductase, mevalonic acid, at a dosage level of 500 mg/kg b.i.d. A diet supplemented with 0.5% or 1.0% cholesterol had no effect on the teratogenicity of mevinolinic acid. Teratology studies in rats with a dihydroxyheptanoic acid derivative of mevinolin, a compound 1/700 as potent as mevinolinic acid as an inhibitor of HMG-Co A reductase, and dihydromevinolinic acid, an inhibitor of this enzyme comparable in activity to mevinolinic acid, indicated that the teratogenicity of these compounds was related to their relative enzyme inhibitory activity. The dihydroxyheptanoic acid derivative was not teratogenic at doses as high as 150 mg/kg b.i.d.; in contrast, when dihydromevinolinic acid was administered at 50 and 100 mg/kg/day, its potency as a teratogenic agent was comparable to that of mevinolinic acid. These studies demonstrated that inhibitors of HMG-CoA reductase produced terata in rats and that the teratogenic effects could be antagonized by coadministration of the enzyme product, mevalonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1983

Projections from the pretectal complex to the thalamic lateral dorsal nucleus of the cat.

The subcortical projections to the lateral dorsal nucleus (LD) of the cat thalamus were studied with retrograde transport techniques. Deposits of horseradish peroxidase (HRP) or fluorescent tracers were placed unilaterally in LD of adult cats, using electrophoretic or pressure injection techniques. Following post-injection survival periods of 1, 2 or 3 days, HRP retrogradely labeled cells were identified in sections reacted with benzidine dihydrochloride; fluorescent labeled cells were identified by fluorescent microscopy. Injections in LD result in retrogradely labeled neurons in all nuclei of the pretectal complex, including the nucleus of the optic tract (NTO), the posterior pretectal nucleus (NPP), the anterior pretectal nucleus (NPA), the pretectal olivary nucleus (NOL), and the medial pretectal nucleus (NPM). Small electrophoretic injections of HRP were used to investigate a possible topographic organization of the pretectal projections. Results from a variety of injection sites indicate only a subtle rostral-caudal gradient. That is, small injection sites in rostral LD result in retrograde labeling of neuron somata in the rostral parts of NTO, NPA and NPP, and throughout NPM. Injections in caudal LD result in labeled cells more caudally situated in NTO, NPA, NPP, and throughout NPM. Injections in the pulvinar (Pul) also result in retrogradely labeled cells in the pretectal complex, particularly NTO, NPP, and NOL. Experiments with injections of distinguishable fluorescent tracers in LD and Pul reveal that many more cells project to Pul than to LD. These experiments also reveal that while neurons that project to LD are intermingled with neurons that project to Pul, the two projections originate from separate subpopulations of cells. These results are discussed in regard to phylogenetic comparison of pretectal projections and subcortical pathways of sensory input to the limbic system.

Afferent Pathways↗
PubMed1982

Diencephalic projections from the pontine reticular formation: autoradiographic studies in the cat.

Ascending projections to the diencephalon from the pontine reticular formation were studied in the cat by autoradiographic techniques. Projections from both rostral and caudal pontine regions ascend to the caudal diencephalon and divide into two components; a dorsal leaf terminates primarily in the thalamic intralaminar complex and a ventral leaf terminates in the subthalamic region. The relative densities of the two terminal regions vary with the injection site. Fibers originating in the caudal pons (nucleus reticularis pontis caudalis) terminate relatively heavily in the intralaminar nuclei of the dorsal thalamus, particularly the centre median, central lateral, central dorsal and paracentral nuclei, and also the dorsal medial nucleus. Relatively sparse termination occurs in the subthalamic region. In contrast, fibers from the rostral pons (nucleus reticularis pontis oralis) terminate relatively heavily in the subthalamic region, including the zona incerta, the fields of Forel, the ventral part of the thalamic reticular complex, and the lateral hypothalamus. Relatively sparse termination occurs in the dorsal thalamus, but includes the centre median, parafascicular, central lateral, paracentral and dorsal medial nuclei. These data are discussed with regard to reticular control of forebrain activity and the role of the classic dorsal and ventral components of ascending reticular projections.

Afferent Pathways↗
PubMed1982

Double labelling of neuronal somata by [3H]uridine and horseradish peroxidase: a technique to demonstrate two-stage connections with the light microscope.

A new technique is described that may demonstrate two-stage connection at the light microscopic level. Anterograde transneuronal transport of [3H]uridine is used in conjunction with retrograde transport of horseradish peroxidase (HRP). The two compounds are injected separately into different brain regions. Under conditions of proper controls, neuron somata that are double labelled are interpreted as receiving an afferent projection from the region injected with [3H]uridine and sending an efferent projection to the region injected with HRP. Thus, the technique can demonstrate two-stage connections in the nervous system.

Animals↗
PubMed1982

Exposure of rats to lead nitrate in utero or postpartum; effects on morphology and behavior.

Female rats were administered lead (Pb), as the nitrate salt, on day 17 of pregnancy (5 or 25 mg/kg i.v.) or throughout lactation (5 or 25 mg/kg/day p.o.). There were adverse effects on weights of females receiving Pb on day 17. At 25 mg/kg i.v. gestation was significantly prolonged. In both groups treated intravenously, average pup weight on day 1 postpartum was significantly reduced and there was a significantly higher mortality than in controls, and hydrocephalus occurred. Survival rate and weight gain of pups from dams that received Pb throughout lactation was not different from controls. Brain weights and histomorphology of all groups was normal. Behavior in male offspring, as measured by open-field activity, rotorod or passive avoidance tests, was unaffected by exposure to Pb.

Abnormalities, Drug-Induced↗
PubMed1981

Organization of corticothalamic projections from parietal cortex in cat.

Corticothalamic projections from areas 5a, 5b, and 7 of cat parietal cortex were studied with autoradiographic techniques. Each cortical area was identified by its cytoarchitectural characteristics and the patterns of termination were related to the thalamic nuclear groups. Injections of 3H-leucine in cortical area 5a were associated with terminal labeling primarily in the spinal recipient zone of the ventral lateral nucleus (VLsp) and the medial division of the posterior group (POm). The corticothalamic projections of area 5a are loosely topographically organized; medial parts of 5a project heavily to rostral and lateral parts of VLsp and sparsely to POm, while lateral parts of 5a project to more medial and caudal parts of VLsp and heavily to POm. Cortical area 5b projects primarily to the rostral portions of the lateral posterior nucleus (LP). These projections also appear to be topographically organized. The part of area 5b on the marginal gyrus projects to more ventral parts of rostral LP, while area 5b on the middle suprasylvian gyrus projects to more dorsal and lateral parts of rostral LP. Cortical area 7 projects to LP and the pulvinar (Pul). Rostral parts of area 7 project heavily to dorsal and lateral parts of LP and lightly to Pul; more caudal portions of area 7 projects relatively more heavily to Pul. The reticular, central lateral, and paracentral nuclei also receive projections, especially from the suprasylvian gyrus. The results are discussed with regard to putative sensory response characteristics of these cortical areas and to general thalamocortical organization.

Animals↗
PubMed1981

Thalamic connections with limbic cortex. I. Thalamocortical projections.

The thalamocortical projections to limbic cortex in the cat have been studied with retrograde and anterograde axonal transport techniques. Five limbic cortical areas were identified on the basis of cytoarchitecture. The five areas are the anterior limbic area, the cingular area, the dorsal and ventral retrosplenial areas, and the presubiculum. Each of these cortical areas received small injections of horseradish peroxidase, and the afferent thalamic nuclei were identified by retrograde labelling of cells. The cortical projection of each of the anterior thalamic nuclei and the lateral dorsal nucleus was determined autoradiographically. Each of the anterior thalamic nuclei and the lateral dorsal nucleus projects to limbic cortex by two pathways. One group of fibers leaves the rostral thalamus by the fornix, pierces the corpus callosum, joins the cingulate fasciculus to reach limbic cortex. The other group travels through the lateral thalamic peduncle and internal capsule. The anterior ventral nucleus projects primarily to the dorsal retrosplenial area, particularly to layer I, the deep portion of layer II, and superficial portion of layer III. Sparse projections also exist to the ventral retrosplenial area, the cingular area, and the presubiculum. Very sparse projections to the anterior limbic area are seen. The anterior dorsal nucleus projects primarily to the ventral retrosplenial area, particularly layers I, the deep portion of layer II, and superficial layer III. sparse projections exist to the dorsal retrosplenial area and presubiculum, but apparently no projections exist to the cingular or anterior limbic area. The anterior medial nucleus projects primarily to layers I and superficial III of the ventral retrosplenial area. sparse projections exist to each of the other limbic cortical areas. The lateral dorsal nucleus projects extensively onto limbic cortex. Prominent projections occur to layer I, the external granular layer and lamina dessicans of the presubiculum, layers I and III-IV of the dorsal retrosplenial area, and layers I, III, and IV of the cingular area. Sparse projections occur to the ventral retrosplenial area and the anterior limbic areas. Thalamocortical projections also originate in the midline and intralaminar nuclei including the central medial, reuniens, rhomboid, paracentral, central lateral, and central dorsal nuclei. These data indicate that the anterior thalamic nuclei project upon limbic cortex in a complex manner. Further, the projections to limbic cortex from the anterior nuclei overlap with projections from the lateral dorsal nucleus. This overlap of thalamic projections onto limbic cortex suggests a convergence of information from nonprimary sensory systems with information from the classical limbic system.

Animals↗
PubMed1981

Thalamic connections with limbic cortex. II. Corticothalamic projections.

The corticothalamic projections from the cat limbic cortex have been investigated with anterograde and retrograde axonal transport techniques. Five limbic cortical areas-the anterior limbic area, the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum-were identified on the basis of their cytoarchitecture. Emphasis was placed on determining the laminar distribution of the cells of origin of the efferent projections, the projection pathways, and the sites of termination within the thalamus. Projections to the thalamus originate in layers V and VI of limbic cortex. In the cingular region the cells of origin are predominantly in layer V and to a lesser extent in layer VI, while the majority of cells projecting from the more caudal retrosplenial areas and presubiculum are in layer VI. There are two fiber pathways from each cortical area to the thalamus. One system of fibers passes through the internal capsule and lateral thalamic peduncle, and a second system travels in the cingulate fasciculus before piercing the corpus callosum to join the postcommissural fornix. The lateral dorsal nucleus and the anterior nuclear group, including the anterior dorsal, anterior ventral, and anterior medial nuclei, are the major thalamic recipients of projections from limbic cortex. Corticothalamic projections also terminate sparsely in the midline and intralaminar nuclear complex, including the central lateral, central dorsal, paracentral, central medial, rhomboid, and reuniens nuclei. Projections from the anterior limbic area project predominantly to the anterior medial, central lateral, and paracentral nuclei. the anterior ventral nucleus, anterior medial nucleus, and lateral dorsal nucleus are the major thalamic recipients of projections from the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum. It appears that the anterior dorsal nucleus receives afferents only from the dysgranular retrosplenial area. Bilateral cortico-thalamic projections were found in the anterior medial, dorsal medial, central lateral, central medial, paracentral, and reuniens nuclei.

Animals↗
PubMed1981

Patterns of habituation to electrical stimulation of reticular and auditory pathways.

Patterns of habituation of the orienting response to electrical stimulation of midbrain, thalamus, and cortical components of the primary auditory pathway and the ascending reticular system were studied in awake, freely mobile cats. Individual orienting responses to high-frequency stimulation of structures in the auditory pathway could not be distinguished from orienting responses to stimulation of reticular structures. However, with repeated presentations of the stimulus, the orienting response to auditory pathway stimulation habituated significantly faster than did the orienting response to stimulation of structures in the ascending reticular system. Within the auditory pathway, orienting to stimulation of the inferior colliculus, the medial geniculate body, or primary auditory cortex did not result in distinguishable patterns of habituation. Stimulation of parietal cortex resulted in habituation that occurred significantly slower than habituation to auditory cortex stimulation, and significantly faster than habituation to stimulation of the midbrain reticular formation or the centre median nucleus of the thalamus. These results are discussed with regard to a hypothetical arousal system that includes the brain stem reticular formation, the intralaminar nuclei of the thalamus, and parts of the parietal cortex.

Animals↗