Area Of Rabbits Research Articles

Supplementation of the Black Rice Outer Layer Fraction to Rabbits Decreases Atherosclerotic Plaque Formation and Increases Antioxidant Status

The influence of the supplementation of black and white rice outer layer fractions on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in rabbits. Male rabbits (n = 32) were randomly divided into four groups. They were fed nonpurified diet (normal group), a lard (3.5 g/100 g) with high cholesterol (0.5 g/100 g) diet (HC group); the HC diet with 5 g/100 g white rice outer layer fraction (WRF group); or the HC diet with 5 g/100 g black rice outer layer fraction (BRF) for 2 mo. Blood samples were collected for determination of lipid concentration and oxidative and antioxidative status variables, and aortae were taken for the assessment of atherosclerotic plaques. The atherosclerotic plaque area in rabbits fed the BRF diet was 66% lower than that of the HC or WRF rabbits (P < 0.001). Supplementation of the black rice outer layer significantly (P < 0.05) lowered aortic 8-hydroxy-2'-deoxyguanosine (8-OHdG) (-52%, -44%) compared with the WRF or HC diets (P < 0.05). There were no differences in aortic 8-OHdG levels between rabbits fed the BRF and normal diets. The BRF diet significantly (P < 0.05) decreased the malondialdehyde (MDA) level of serum (-37%) and aortic artery (-50%) compared with the WRF diet. There were no differences in the concentrations of serum total cholesterol (TC), LDL cholesterol (LDL-C), HDL-C or the ratio of apoprotein (apo)I/apoB among the HC, WRF and BRF groups. Similarly, there were no differences in the serum vitamin E concentration and erythrocyte and aorta superoxide dismutase (SOD) activities among rabbits fed these diets. The serum concentration of most fatty acids except 18:1 did not differ between the WRF and the BRF groups. We conclude that the inhibition of atherosclerotic plaque formation derived from the black rice outer layer fraction in rabbits might be mediated by antioxidative or anti-inflammatory effects.

In vivo uptake of radiolabeled MDA2, an oxidation-specific monoclonal antibody, provides an accurate measure of atherosclerotic lesions rich in oxidized LDL and is highly sensitive to their regression.

To determine whether labeled antibodies against oxidized LDL (OxLDL) offer advantages for quantifying atherosclerosis, we compared in vivo aortic uptake of (125)I-labeled MDA2, a monoclonal antibody against malondialdehyde-lysine epitopes), atherosclerotic surface area, and aortic weight in Watanabe heritable hyperlipidemic and New Zealand White rabbits and in low density lipoprotein receptor-deficient (LDLR(-/-)) and apolipoprotein E-deficient (apoE(-/-)) mice. Absolute and specific uptakes of (125)I-MDA2 were significantly greater in plaque than in normal aortas. Uptake of (125)I-MDA2 significantly correlated with aortic weight and percent atherosclerotic surface area in rabbits and mice. To assess whether (125)I-MDA2 uptake reflects changes in lesion content of OxLDL, in a separate study, extensive atherosclerosis was induced in 4 groups of LDLR(-/-) mice by feeding them a high fat/cholesterol diet for 6 months. A baseline group was euthanized at this time. The remaining groups were fed "regression" diets (chow or chow+1% vitamin E+0.05% vitamin C) or the high fat/cholesterol diet for 6 more months. When atherosclerosis was measured as percent surface area or aortic weight, there was strong progression in the high fat/cholesterol group, moderate progression in the chow group, and no progression in the chow+vitamin E+vitamin C group compared with the baseline group. The (125)I-MDA2 method also yielded a significant increase in atherosclerosis in the high fat/cholesterol group but significant decreases in the chow and chow+vitamin E+vitamin C groups. Immunocytochemistry showed fewer oxidation-specific epitopes in lesions from the chow and chow+vitamin E+vitamin C groups. Thus, the uptake of (125)I-MDA2 correlates well with traditional measures of atherosclerosis but also reflects reduced plaque OxLDL content after hypocholesterolemic intervention.

Medial Geniculate Lesions Block Amygdalar and Cingulothalamic Learning-Related Neuronal Activity

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)+] to avoid a foot shock, and they learn to ignore a different tone (CS-) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CS+ than to the CS-. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas.

Trigeminal Inputs to Eyeblink Motoneurons in the Rabbit

The rabbit nictitating membrane and eyeblink response is widely used in studies of classical conditioning. Eyeblinks involve coordinated activation of the orbicularis oculi motoneurons (OOcVII) and accessory abducens motoneurons (AccVI) which close the external eyelids and nictitating membrane, respectively, and inhibition of levator palpebrae motoneurons (LPIII) whose activity raises the upper eyelid. The identification of blink interneurons that may coordinate these responses is an important step in the analysis of mechanisms supporting eyeblink conditioning as they are likely to receive convergent inputs from circuitry associated with learned as well as unlearned responses. We first investigated the distribution of OOcVII motoneurons in the facial nucleus and LPIII motoneurons in the oculomotor nucleus by retrograde tracing of wheat germ-agglutinated horseradish peroxidase (WGA–HRP) injected into the appropriate muscles. We then used an anterograde tracing method to locate trigeminal and paratrigeminal inputs to OOcVII, to AccVI nucleus, and to LPIII. Injections of WGA–HRP were placed into the principal trigeminal nucleus (Vp) and into all divisions of the spinal trigeminal nucleus. We found an area in Vp and the adjacent rostral parts of pars oralis of the spinal trigeminal nucleus that gave clear projections to OOcVII and AccVI motoneurons and adjacent to LPIII motoneurons in the contralateral oculomotor nucleus. We suggest that neurons in this premotor blink area in rabbits can coordinate learned and reflex blink responses involving the external eyelidsandthe nictitating membrane. In addition, there are direct projections from the pars interpolaris and pars caudalis of the spinal trigeminal nucleus to the facial nucleus that may mediate short latency responses of the external eyelid orbicularis oculi muscle alone.

Immunoliposomes and PEGylated Immunoliposomes: Possible Use for Targeted Delivery of Imaging Agents

Liposomes can be made target-specific by immobilizing antibodies on their surface against characteristic components of target organ or tissue. Possible schemes of antibody immobilization on liposomes are briefly considered. The use of immunoliposomes for the targeted delivery of diagnostic and therapeutic agents within the cardiovascular system is discussed. Immunoliposomes are shown to be suitable carriers for targeting blood vessel injuries, lung endothelium, and myocardial infarction. The role of polyethylene glycol in the preparation of long-circulation liposomes is investigated, and a hypothesis explaining the mechanism of polymer protective action in terms of physicochemical properties of diluted polymeric solutions is suggested. Polyethylene glycol-coated liposomes are investigated as possible carriers of imaging agents for gamma and MR visualization of different areas of interest in the body, including lymph nodes. The possibility of simultaneous immobilization of protective polymer and antibody on the liposome surface is proved, and the long-circulating targeted immunoliposomes are used for the targeted delivery of radiolabel to necrotic areas in rabbits with experimental myocardial infarction.

Modulation of neuronal firing in the medullary solitary complex by electrical stimulation of the hypothalamic defense and vigilance areas in rabbits

The present study sought to establish functional connections between two regions in the hypothalamus associated with the cardiorespiratory concomitants of affective behavior, and neurons in the dorsal medulla thought to be involved in the mediation of the baroreceptor reflex. Single cell recordings were made in the solitary complex of the medulla (nucleus of the tractus solitarius and dorsal vagus nucleus) of anesthetized rabbits. An attempt was made to modulate the activity of these neurons by electrically stimulating two hypothalamic sites: the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA). Responses of solitary complex neurons to a bolus injection of phenylephrine and an injection of physiological saline in a blind sac preparation were assessed in order to test for baroreceptor input. Electrical stimulation of the HDA or the HVA was found to decrease the firing rate of most solitary complex neurons that responded to hypothalamic stimulation. The cells that did show an increase in firing rate were responding to HVA stimulation. Ninety-two percent of the neurons in the solitary complex that responded to HDA or HVA stimulation were also affected by baroreceptor activation. The connections between the HDA, HVA and the solitary complex may account, in part, for the distinctive patterns of cardiorespiratory responses observed when stimulating these two hypothalamic regions.

Evolution of excimer laser corneal surgery

Interest in the potential of the excimer laser for refractive surgery was generated by a series of experiments performed in IBM's T.J. Watson laboratories. The development of photoablative decomposition was applied to corneas with immediate implication for corneal refractive control. Scientific investigations demonstrated that submicron erosion ablation of material was possible without damage to remaining tissues. After refinement of the beam and analysis of thresholds, we subsequently demonstrated that healing of large ablated areas in rabbits and then primate eyes would occur without scar formation or loss of transparency. This prompted a number of commercial efforts to develop this device for both refractive and general corneal surgical applications. The early clinical investigations show that a predictable refractive change could be induced in a cornea and this change was stable over many months. Furthermore, the transparency of the cornea was unimpaired. These favorable early results have led to a number of clinical investigations of excimer laser corneal surgery including refractive keratectomy, a direct laser keratomileusis.

Conjugation of unit activity in visual and sensorimotor neocortical areas of rabbits during calm wakefulness and pseudoconditioning.

1. The number of pairs of neurons of the visual and sensorimotor regions of the cortex working in correlation in rabbits during calm wakefulness is consistently less (35%) than during pseudoconditioning; during pseudoconditioning, the number of such pairs were the same for a presentation of flashes of light in random order accompanied by electrocutaneous stimulation (49%) or for a presentation of sound accompanied by electrocutaneous stimulation (50%). The constant level of pairs functioning in conjugation during calm wakefulness and pseudoconditioning was maintained for the most part by different pairs of cells at different moments in time. 2. During calm wakfefulness as opposted to a CR, the numbers of cross-correlation histograms with broad central peaks indicating the effect of a common source upon the neurons being recorded was fewer. 3. During calm wakefulness and during pseudoconditioning, the number of pairs with up to 120-msec delays in the discharges of neurons of the visual region after those of the sensorimotor region and up to 120-msec delays in the discharges of the sensorimotor region region after the visual were equal. 4. The data obtained on the delays in discharges of neurons during calm wakefulness and pseudoconditioning indicate that a forestalling of the discharges of the neurons of the visual region by discharges of the sensorimotor region are only characteristic of cases when the given regions are the cortical representations of the conditioned and unconditioned stimuli during a CR.

The effect of fixation on corneal endothelial cell dimensions and morphology in scanning electron microscopy.

Soft tissue specimens shrink during fixation, dehydration and critical point drying when prepared for scanning electron microscopy (SEM). This can cause serious artifacts not only in 'compact' tissues but especially in hollow structure, like the eye, where the chambers are lined by delicate layers such as the corneal endothelium. In this study various glutaraldehyde and formaldehyde fixations at different concentrations with or without 5% sucrose were tested. Dimensional as well as morphological changes of rabbit corneal endothelial cells were evaluated. The mean surface diameter and area of rabbits' central corneal endothelial cells were measured first in vivo by specular microscope. Thereafter the same corneas were fixed in 9 different solutions and processed for scanning electron microscopy. The surface structure of the same endothelium was then photographed with SEM. The cell dimensions were remeasured. According to our results 1.25% or 2.50% glutaraldehydes without sucrose gave the best surface preservation and caused the least shrinkage.

Monocular pattern discrimination performance in rabbits with unilateral interruption of the middle cerebral artery

Rabbits were tested binocularly and with each eye separately, in pattern discriminations sensitive to the removal of the visual cortex opposite the exposed eye before and after the middle cerebral artery was unilaterally coagulated. Following surgery, the rabbits were not impaired in performing the discriminations with either eye; nor were any pathological changes found in the hemisphere in which surgery was performed. These findings imply that deficits in performing tasks dependent on the integrity of the visual cortical areas in rabbits may require interruption of the posterior and middle cerebral arteries, both of which supply the visual cortical areas.

Pharmacokinetics of doxorubicin and its metabolite doxorubicinol in rabbits with induced acid and alkaline urine.

The pharmacokinetics of doxorubicin in rabbits preloaded either with ammonium chloride or sodium hydrogencarbonate have been investigated following single IV administration of 5 mg/kg. Plasma samples and urine collections were obtained over 3 h following administration, and were assayed in duplicate for doxorubicin and its main metabolite doxorubicinol by reversed-phase high-pressure liquid chromatography. The plasma concentration of doxorubicin was fitted to an open two-compartment model. The areas under the plasma concentration-time curves (AUC) of doxorubicin in rabbits with alkaline urine were approximately half the areas in rabbits with acid urine. A pharmacokinetic analysis indicated an increase in the central volume of distribution, which is interpreted as an increase in tissue permeability in the alkaline state, due to the acid-base properties of the doxorubicin molecule. The renal excretion of doxorubicin and doxorubicinol was quantitatively similar in the two groups of rabbits. The total renal excretion of anthracyclines during the experiment was calculated to approximately 6% of the administered dose. The clearances of doxorubicin were initially three times higher than inulin clearance, but approximated this value at the end of the experiment. The renal handling of doxorubicin in the rabbit is explained by glomerular filtration followed by tubular secretion and finally by a reabsorption mechanism with limited capacity.

Tofisopam, a new 2,3-benzodiazepine. Inhibition of changes induced by stress loading and hypothalamic stimulation.

Effects of tofisopam, a new 2,3-benzodiazepine compound, were investigated on the following: gastric ulceration, induced by water-immersion stress in normal rats and by immobilization stress in olfactory-bulbectomized (OB) rats; and propulsion of the small intestine caused by water-immersion stress in rats and autonomic responses to electrical stimulation of the hypothalamus in rabbits. In the latter, the results were compared with those of diazepam and gamma-oryzanol. Tofisopam (30 and 100 mg/kg, po) significantly inhibited the gastric ulceration induced by water-immersion stress in normal rats in a dose-dependent manner. Immobilization-stress loading increased the incidence and average index of gastric ulceration in OB rats, compared with nonstressed rats. Tofisopam (100 mg/kg, po) significantly inhibited the gastric ulceration induced by stress loading in OB rats. Water-immersion stress loading induced a significant increase in intestinal propulsion in rats. This increase was reversed to control levels by tofisopam (100 mg/kg, po). Tofisopam (1.0 mg/kg, iv, or 0.1 mg/kg by intracerebrospinal injection) inhibited the constriction of ear microvessels, the decrease in earlobe temperature, and mydriasis induced by electrical stimulation of the medial hypothalamic area in rabbits. However, diazepam and gamma-oryzanol failed to inhibit the autonomic responses to medial hypothalamic stimulation. From these results, it can be concluded that tofisopam restores the autonomic abnormality induced by stress loading possibly via intervention in the central autonomic area, i.e., the hypothalamus, by an action different from that of diazepam.

Effect of stimulation of cortical association areas in rabbits on evoked potentials and unitary responses in the visual cortex.

1. The cortical association areas exert an important influence on EP and single unit activity in the visual cortical projection area. 2. Stimulation of the anterior cortical association areas leads to lengthening of the inhibitory pause and to a decrease in the late discharges in the response of visual projection neurons to flashes, and this is reflected in a significant reduction of the secondary negative-positive complex of the EP. It can be postulated on the basis of these data that the anterior association cortex has an inhibitory influence on the principal neurons of the visual cortex receiving the afferent signal. 3. Stimulation of the posterior association cortex causes lengthening and deepening of the inhibitory pause in unit activity and an increase in the late discharges in the response of visual cortical neurons to flashes; there is a corresponding enlargement of the secondary negative-positive complex of the EP. On the basis of these results it is postulated that the posterior association cortex has a facilitatory influence on the recurrent inhibition system in the visual cortex.

A Comparative Study of theIn VitroandIn VivoRelease of Dexamethasone from a Spray-On Bandage and Timed Release Aerosol

AbstractThe formulation of several dexamethasone topical delayed release aerosol preparations was studied. Ethylcellulose and tributyl citrate were the film-forming agent and plasticizer, respectively, for the spray-on bandage formulation. The aerosol timed release preparation contained dexamethasone microcapsules suspended in a fluorocarbon aerosol propellant by isopropyl myristate and fumed silica. Both preparations were evaluated using an in vitro method which measured the release of dexamethasone hourly for eight hours. In vitro studies showed that each of the formulations delayed the release of dexamethasone. In the in vivo tests aerosols were sprayed on the unabraded back area of rabbits and the increased 17 - hydroxycorticosteriod urine levels at 24, 48, and 72 hours indicated dexamethasone absorption. In vivo studies indicated that absorption did not occur with the timed release preparation containing dexamethasone microcapsules. However, dexamethasone from the spray-on bandage preparation was abs...

Absorption of a non-ionic contrast agent from cerebrospinal fluid to blood.

Intrathecal injection of a non-ionic contrast agent in the lumbar area of rabbits resulted in: (1) a rapid rise in blood iodine level with a maximum after 23-46 min; (2) low concentrations in cisterna magna during the observation period (24 h); and (3) complete or almost complete disappearance of visible contrast medium on the radiographs within 30 min. This indicates that after injection in the lumbar area of the rabbit most of the contrast medium absorption takes place from the lumbar area. Similar injections in cisterna magna showed the following: (1) a slow rise in blood level with a maximum after 150-275 min; (2) little or no disappeared of visible contrast medium on the radiographs within the first hour. This indicates that in the rabbit the absorption from the subarachnoid space of the spine takes place at different rates dependent on the level at which the injection has been made and the area of deposition of contrast medium.

Carbohydrate metabolites in rabbit hereditary ataxia.

GLYCOGEN deposits have been demonstrated with light and electron microscope in the hindbrain areas of rabbits affected with hereditary ataxia. 1,2 This raises the possibility that the underlying specific hereditary defect is in some way related to carbohydrate metabolism. Consequently, a quantitative study has been made of glycogen and of major intermediates of glycolysis in brains of ataxic rabbits. In order to assess the glycolytic capacity and metabolic status, these substances, as well as adenosine triphosphate (ATP) and phosphocreatine, were measured in two samples of tissue from each animal. One sample was frozen as quickly as possible after removal from the animal; the second sample was frozen about one minute later, ie, after a measured period of ischemia. Three enzymes concerned with glycogen metabolism and two enzymes of the pentose pathway were also measured. The lesions of hereditary ataxia develop in a predictable pattern. 3 To take advantage of this,

Antitoxin-Localizing Method in Determining Antilocalization in X-Irradiated Areas of Rabbits

Recent studies indicate that X-irradiation reduces the localization of proteins or organisms injected in the skin of rabbits. Thus, Kahn et al. showed by means of the antitoxin-localizing method (1) that a dose of subcutaneously injected diphtheria antitoxin that does not protect most normal rabbits from a lethal dose of homologous toxin becomes protective if injected in an irradiated area. Apparently the antitoxin becomes localized in the injected area of the normal rabbits and does not reach the toxin fast enough for neutralization, but it is not localized in the irradiated area, from which it rapidly reaches and neutralizes the toxin. This observation of the antilocalizing tendency of irradiation was corroborated (2) by the injection of virulent staphylococci in irradiated and in nonirradiated areas of rabbits. The irradiated areas showed little or no lesions, indicating the escape of the organisms from them, whereas the nonirradiated areas showed severe lesions, indicating that the organisms became localized in those areas. Antilocalization due to irradiation was reported more recently after the use of subcutaneous implants of horse gamma globulin in irradiated and in nonirradiated areas of rabbits (3). The globulin escaped from the implants to a greater degree from the irradiated than from nonirradiated areas. This report will discuss the antitoxin-localizing method as it applies to irradiation and will present experimental data on some factors that aid in the detection of antilocalization after irradiation.

Movement of Horse Gamma Globulin out of and Isologous Proteins into Paper Implants in Focally X-Irradiated Rabbits

On rabbits unilaterally exposed to 930 to 1000 r of focal x-irradiation on two separate areas, 15 to 25 r was measured on the opposite side of the animals. When 274 mu g of N/sub 2/ per 0.2 ml of a purified horse gamma - globulin preparation was subcutaneously implanted for 48 hours in focally irradiated areas of rabbits, these areas showed decreased localization (increased protein escape) for the initial 24 hours after irradiation. Such antilocalizing activity of irradiation on subcutaneous areas decreased when measured at 7 and 14 days after exposure. In the study of the phenomena of localization and antilocalization as affected by irradiation, the quantitative results herein obtained by subcutaneous implants of heterologous protein parallels the results obtained by a toxin-antitoxin system. This finding indicates that the use of subcutaneous implants offers a method for more exacting quantitative studies of localizing phenomena. From the comparative absorption rates of heterologous and isologous proteins, this study suggests that, although irradiation can increase the permeability of an area, consideration must be given to the biological relationship between an injected foreign protein and the host proteins. Proof that an increase in permeability is the predominant radiation effect should consider the differentialmore » innate ability of an animal to localize foreign substances. (auth)« less

Irradiation and Tissue Immunity II. Response to Injection of Staphylococci in X-Irradiated Skin Areas of Rabbits

Twenty-four hrs after 1000-r x irradiation of a small area of the skin of rabbits, they were injected with a suspension of staphylococci subcutaneously in the irradiated area and in a nonirradiated control area. Localized lesions were most marked in nonirradiated areas and in some animals no visible lesions were noted in irradiated areas. The mild inflammatory lesions in irradiated areas corroborate the point of view, that irradiation is anti-inflammatory. The reason for mild lesions must be the reduced localization of staphylococci in irradiated areas and their escape from those areas. It is suggested that the antilocalizing property of irradiation is probably the basis for the antiinflammatory action. When the concentration of organisms injected in the irradiated area was high (10 billion), septicemia and death of the rabbits occurred, presumably as a result of the antilocalizing property of irradiation, which permitted the escape of the organisms from the injected area. In animals injected in irradiated areas with either 0.5 or 5 billion organisms, no septicemia was observed, presumably because of the high natural immunity of rabbits to staphylococci. (TCO)

A central control mechanism of the adrenocortical function: with special reference to the functional regulation within the hypothalamus.

It may be concluded that the results based on experimentations in cats, rabbits, mice and dogs by using various kinds of stimulation or destructive techniques indicate that the areas which are closely related to a regulation of the adrenocortical function in these animals are in the posterior and/or mid-hypothalamus and in the septal area of rabbits. It may be of particular interest that in dogs three different response patterns of the adrenocortical secretory activity were observed by electrical stimulation of various sites of the hypothalamus.