Enhanced alveolar bone loss in a model of non-invasive periodontitis in rice rats.

OBJECTIVE: The rice rat (Oryzomys palustris) develops periodontitis-like lesions when fed a diet rich in sucrose and casein (H-SC). We aimed to establish whether this model can accurately mimic the development of human periodontitis. MATERIALS AND METHODS: For this purpose, 28-day-old rice rats (15/group) were assigned to standard (STD) or H-SC diets and sacrificed after 6, 12, and 18 weeks. Jaws were processed for morphometric, histometric, histologic, histomorphometric, and micro-CT analyses. RESULTS: We found a progressive increase in horizontal alveolar bone loss (ABL) with age in maxillae of rats fed the STD diet as determined by morphometry. The H-SC diet exacerbated horizontal ABL at the palatal surface at 12 and 18 weeks. Furthermore, increased vertical ABL was detected in mandibles and maxillae of rats fed the H-SC diet for 12 and/or 18 weeks by histometry and micro-CT. Remarkably, the H-SC diet significantly increased bone remodeling at the interproximal alveolar bone of mandibles from rats fed for 6 weeks, but not in those fed for longer periods. CONCLUSIONS: These findings indicate that the H-SC diet induced a transient increase in alveolar bone remodeling, which is followed by ABL characteristic of moderate periodontitis.

Characteristics of carbon dioxide-induced antinociception.

This lab previously showed that brief inhalation of high concentrations of CO2 results in a prolonged, moderate antinociception with characteristics of a nonopiate, hormonal mechanism. To further characterize and optimize this response, the effect of a variety of methodological, biological, and stress-related manipulations were studied. No significant differences were found in the CO2-induced response between animals that were tested during different portions of their diurnal cycles, in rats that were unhandled or habituated to nociceptive testing conditions, in male vs. female rats, or in animals of differing weights. Additionally, restraining animals prior to CO2 exposure induced a hot plate antinociceptive response that was not different from the response produced by CO2 alone. In contrast, on the tail flick test, a CO2 -restraint interaction both increased and decreased the response at different times. The present findings show that CO2 antinociception: a) is a reliable phenomenon not altered by a variety of methodological and biological conditions, and b) has characteristics of a novel, stress-mediated antinociceptive response.

Lead toxicity via arachidonate signal transduction to growth responses in the splenic macrophage.

Lead chloride modulated the macrophage cell surface growth signal-transduced, lipid second messenger prostaglandin E2 (PGE2), concomitant with cell differentiation. In virgin macrophage, PGE2 was increased by lead in a dose-dependent manner, suggesting suppression of the immune function (inversely regulated by PGE2). Upon stimulation by bacterial endotoxin, lead-treated cells displayed decreased PGE2 with immune augmentation as tested by zymosan particle ingestion. These effects were simulated by a glutathione synthesis inhibitor around 10 microM lead, and by cycloheximide around 50 microM lead, suggesting a mechanism similar to viral infection.

Premortem biodistribution of radioactivity in the rat: measurement of blood and tissue activity of tracers used in clinical imaging studies.

Radioactive tracers are used in nuclear medicine imaging studies to detect sites of human disease. Use of animal models helps to establish tracer biodistribution kinetics and, thus, is critical to the early testing of radiopharmaceuticals. We developed a method to characterize the premortem temporal, spatial, and compartmental biodistribution of tracer molecules in the rat and used this method to study three tracers of potential value in detecting thromboembolic disease. Dynamic gamma scintigraphy was used to determine the spatial and temporal distribution of 99mTc-labeled IgG antifibrin antibody, Fab' fragment of antifibrin, and oxidized human serum albumin (OHSA). The blood pool compartment within each tissue was determined from the biodistribution of 131I-labeled bovine serum albumin injected prior to termination. The biodistribution of the blood compartment was maintained by immediately freezing the rat carcass in isotonic saline. Three-dimensional maps of tracer distribution in the tissue and blood compartments were then constructed from cross sections of the frozen tissue. These maps were used to relate necropsy tissue counts to premortem scintigraphic images. Over a 60-min interval after administration of tracer via a tail vein, significant differences in biodistribution were evident. The IgG remained within the blood pool, but there was rapid blood clearance of the OHSA molecules by the kidney and liver. The Fab' molecules were cleared more slowly by the kidney; Fab' molecules were found in the extravascular spaces, whereas IgG and OHSA were not found. The kinetics of OHSA and Fab' in organ regions paralleled changes in the blood compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged antinociception following carbon dioxide anesthesia in the laboratory rat.

In the laboratory rat, inhalation (30 s) of high (> 70%) CO2 concentrations resulted in short-term (1-3 min) anesthesia, followed by a prolonged (up to 60 min) mild antinociception. Exposure to 100% CO2 resulted in significant thermal (hot-plate, 52 degrees, and tail-flick) and mechanical (tail-pinch, 886 g force) antinociception. Control animals, placed in the same chamber filled with air, showed no such effects. Rats exposed to 70% CO2 exhibited effects on the hot plate comparable to those seen after inhalation of 100% CO2, indicating that the response is not due to CO2-induced hypoxia. Additionally, recovery from halothane-induced anesthesia of comparable duration did not result in antinociception, confirming that anesthesia alone is not sufficient to produce the effect. Pretreatment with the opiate antagonist naltrexone (0.1-10 mg/kg i.p.) did not diminish the CO2-induced antinociception, suggesting that endogenous opioids are not obligatory in the mechanism of this response. Furthermore, hypophysectomy abolished hot-plate antinociception in animals exposed to 100% CO2 while sham-treated controls exhibited a pattern of hot-plate responses similar to that reported above. Taken together, these findings show that: (1) recovery from CO2-induced anesthesia results in a prolonged mild antinociception, detectable with thermal and mechanical nociceptive tests; and (2) this response may represent a novel from of environmentally induced antinociception, mediated by a non-opiate hormonal substance.

The central connections of the vagus nerve in the ferret.

The vagus nerve mediates emesis due to gastric irritation. The central representation of the vagus in the ferret was studied to establish how the nerve is connected to areas important in the regulation of emesis. In a series of 10 ferrets, WGA-HRP injections (10 microliters) were made into the nodose ganglion. After 24-48 h, animals were reanesthetized and perfused transcardially. A block extending from the pons to upper cervical spinal cord was cut at 50 microns and sections reacted. Nodose ganglion injections of WGA-HRP produced labeling of vagal preterminal segments in the ipsilateral dorsal vagal complex including all subnuclei of the solitary complex where the medial and subgelatinous subnuclei received the densest input, the area postrema (AP), which contained a modest amount of terminal label, and the dorsal motor nucleus of the vagus (DMX). Contralateral terminal label, quantitatively much less, was similarly distributed except that within the solitary complex it was limited to the medial and subgelatinous subnuclei. Retrogradely labeled cells formed ipsilateral dorsomedial and ventrolateral columns, corresponding, respectively, to the DMX and the nucleus ambiguus (including retrofacial and retroambiguus).

Behavioral studies of emetic sensitivity in the ferret.

The ferrets' responsiveness to several known and putative emetic agents was evaluated using a variety of agents that were injected subcutaneously and/or intravenously. Apomorphine was consistently emetic at relatively high doses (100 micrograms/kg) when injected subcutaneously in large male ferrets (> or = 1.4 kg). The responsiveness to apomorphine was anomalous in that subcutaneous injections produced a more consistent response than intravenous ones. In addition, ferrets rapidly become tolerant or tachyphylactic to subcutaneously administered apomorphine. Area postrema ablation, but not abdominal vagotomy, rendered ferrets refractory to the emetic effects of apomorphine. This species, relative to dog and humans, proved to be insensitive to a variety of pharmacologic agents including angiotensin II, gastrin, histamine, Leu-enkephalin, neurotensin, serotonin, and vasopressin. Cisplatin elicited forceful retching and emesis. Emetic responses were obtained with substance P and Met-enkephalin in individual animals but were inconsistent. Sensitivity to DAGO [D-Ala2,MePhe4,Gly-ol5 enkephalin] was variable. Results of this study indicate that the ferret is not an optimal model for all forms of emesis.

Preferential alcoholic embryopathy: effects of liquid diets.

Our initial report of a preferential expression of experimental alcoholic embryopathy affecting the male offspring contiguous in utero to male siblings of Long-Evans rats was based on gavage administration of alcohol to pregnant rats without regard to isocaloric, pair-fed exposure paradigms. In this study, pregnant Long-Evans rats were given 35% ethanol-derived calories (EDC) in one of two different liquid diets: 1) a liquid alcohol diet based on Sustacal, a flavored liquid food formulated for human nutritional standards; and 2) a high-protein liquid rodent diet devised by Lieber and DeCarli (L&D). The diets were administered from day 6 to 15 of gestation. Pregnant rats were pair-fed liquid diets containing 0% EDC, but isocalorically balanced to 35% EDC with either sucrose (Sustacal) or maltose-dextrin (L&D). A fifth group of pregnant rats was given access ad libitum to standard certified laboratory rodent diet and served as free-fed controls. On day 20 of gestation, all pregnant rats were euthanized and the products of conception examined by standard teratologic techniques. Pregnant animals fed Sustacal-based diets consistently consumed fewer calories per kilogram body weight per day from day 6 to 15 of gestation (i.e., they were significantly calorie-deprived during pregnancy) as compared with the standard laboratory-diet-fed controls or those consuming L&D diets. Body weights of rats consuming Sustacal diets (both 0 and 35% EDC) were significantly lower throughout gestation when compared with all other groups. Higher (> 150 mg/dl) blood alcohol levels were attained by rats consuming 35% EDC in Sustacal diet as compared with L&D (100 mg/dl) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

High-moisture diet for laboratory rats: nutrient analysis, growth, and organ weights.

A diet (KSC-25) to be sterilized by irradiation was formulated to contain 66% moisture and to provide the required nutrients for growing rats. Analyses of the irradiated dry diet provided data to evaluate its nutrient content. The diet was evaluated for its ability to supply all nutrients, including water, required by immature rats. Sixteen Sprague-Dawley rats were fed the high-moisture diet with or without access to a water bottle. Rats (n = 16) fed an irradiated purified diet in a meal form with access to a water bottle were the control animals. Feed efficiency, food and water consumption, and growth rate data were collected during the 28-day study. Organ weights were collected on day 28. The test diet met or exceeded the National Research Council (NRC) estimated nutritional requirements for immature laboratory rats. The 66% moisture KSC-25 diet provided all nutrients, including water, required by weanling male Sprague-Dawley rats for growth equivalent to the established purified diet.

High-moisture diet for laboratory rats: complete blood counts, serum biochemical values, and intestinal enzyme activity.

Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n = 32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n = 16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.

Zolantidine-induced attenuation of morphine antinociception in rhesus monkeys.

The effect of zolantidine dimaleate (ZOL), the first brain-penetrating histamine H2 receptor antagonist, was determined on morphine (MOR) antinociception (ANC) in rhesus monkeys. ZOL (0.75 mg/kg, s.c., given every 30 min), completely attenuated the ANC resulting from the lowest dose of MOR tested (1.0 mg/kg), with no effect on the responses to higher doses (3-10 mg/kg). ZOL had no effect on baseline nociceptive responses in the absence of MOR. Taken with previous studies on the pharmacological specificity of ZOL, the ANC properties of histamine, and more extensive studies in rodents, the present results suggest that opiates like MOR relieve pain in primates by mechanisms that include activation of brain H2 receptors.

Electrocardiographic values from clinically normal, anesthetized ferrets (Mustela putorius furo).

Electrocardiograms were recorded from 25 clinically normal male ferrets anesthetized with ketamine and xylazine and from 7 ferrets anesthetized with ketamine alone. Ferrets anesthetized with ketamine alone had excessive salivation, open eyes, muscle tremors, muscle twitching, paddling motions, attempts to stand, and an unstable ECG baseline. Because ketamine/xylazine combination resulted in induction and good muscle relaxation, the ECG had little interference resulting from muscular movement.

Dirofilariasis in a ferret.

An adult male ferret was found to be lethargic and dyspneic. Necropsy revealed 21 worms in the heart, vena cava, and pulmonary artery. The worms were identified as Dirofilaria immitis. Histologic examination of lung tissue revealed numerous microfilariae.