Dysbaric osteonecrosis in mice

The histopathology of dysbaric osteonecrosis and the influence of the number of exposures, compression rate, and obesity on the incidence and latency of the lesion were studied in 438 mice (2505 bones were examined). The animals were subjected to 75 psig air pressure for 2-6 hours (single or multiple exposures). Compression was rapid or stage. Decompression was safe. Osteonecrosis developed in the epiphysis of the tibia and/or femur in 34.1% of obese and in 5.8% of thin animals after a latent period of 2 to at least 12 months. It was concluded that: 1. dysbaric osteonecrosis appears to be independent of decompression sickness; 2. in obese mice the incidence is higher and the latent period shorter; 3. multiple exposures result in higher incidence and earlier lesions than single exposure; 4. the incidence is lower with stage than with rapid compression; 5. the pathogenesis of osteonecrosis may involve several factors (circulatory impairment by extravascular or intravascular bubbles, emboli, thrombi, vasoactive substances, gas-induced osmosis, autoimmunity) acting in concert or in sequence.     

Uncontrollability and unpredictability in post-traumatic stress disorder: An animal model.

The disturbances observed in animals subjected to unpredictable and uncontrollable aversive events resemble posttraumatic stress disorder (PTSD) symptoms and thus may constitute an animal model of this disorder. It is argued that the similarity between animals' symptoms and those of trauma victims may reflect common etiological factors. Relevant experiments in which animals exhibit generalized fear and arousal, discrete fear of a CS, analgesia, and avoidance are reviewed with the view that these manifestations may be analogous to the PTSD symptom clusters of persistent arousal, reexperiencing, numbing, and avoidance, respectively. Finally, animal paradigms are suggested to test the validity of the model, and specific hypotheses are derived from the animal literature regarding trauma variables that are predictive of particular PTSD symptom clusters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An animal model for the behavioral effects of interferon.

Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An animal model for human melanoma

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.     

Phantom auditory sensation in rats: An animal model for tinnitus.

To measure tinnitus induced by sodium salicylate injections, 84 rats were used in a conditioned suppression paradigm. In Exp 1, Ss were trained with a conditioned stimulus/stimuli (CS) consisting of the offset of a continuous background noise. One group began salicylate injections before Pavlovian training, a 2nd group started injections after training, and a control group received daily saline injections. Resistance to extinction was profound when injections started before training but minimal when initiated after training, suggesting that salicylate-induced effects acquired differential conditioned value. In Exp 2, salicylate treatments were mimicked by substituting a 7 kHz tone in place of respective injections, resulting in effects equivalent to salicylate-induced behavior. A 3rd experiment included a 3 kHz CS, and again replicated the salicylate findings. In Exp 4, we decreased the motivational level, and the sequential relation between salicylate-induced effects and suppression training was retained. Findings support the demonstration of phantom auditory sensations in animals. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

An animal model of hypoxia-induced perinatal seizures

Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.     

Schizophrenia, infection and temperature. An animal model for investigating their interrelationships

Cell-free supernatants of 40 Salmonella strains of different serovars were tested for the existence of enterotoxic substances in the rabbit skin permeability factor test, rabbit ileal loop test, tissue culture assays (CHO K1, RTG-2), and baby mouse test. There were differences in the test results between the strains even within the same serovar. Correlation coefficients between the results of different toxin tests were low. It is therefore improbable that the "enterotoxic activity" of Salmonella is caused by only one toxic substance. The activities revealed in the different test systems could not be related to virulence or the epizootiological behaviour of the strains. The in vitro occurrence of the virulence factor "enterotoxin production" is lower for Salmonella than for E. coli and V. cholerae.     

Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model

OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.     

An animal model of leukemogenesis using transgenic mice

The bcr/abl chimeric oncoprotein is considered to be implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate its biological function and the role in leukemogenesis in vivo, we generated transgenic mice expressing p210bcr/abl driven by the metallothionein promoter. Two of six founder mice and the transgenic progeny of one leukemic founder mouse developed leukemias several months after birth. Phenotypically, each leukemic mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode swellings. Pathological examination revealed that leukemic cells were infiltrated in all tissues examined, especially in thymus, spleen, liver, and lymphnode. Expression of the p210bcr/abl transgene product and increased phosphorylation of cellular proteins in leukemic tissues were detected by the Western blot analysis. In addition, the expressed p210bcr/abl protein was demonstrated to possess an enhanced kinase activity by the in vitro immunecomplex kinase assay. These results indicate that hematopoietic precursor cells expressing the p210bcr/abl transgene product acquired a proliferative advantage and eventually developed leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to be an excellent animal model to investigate p210bcr/abl function and its role in leukemogenesis in vivo.     

An animal model of hepatotoxicity associated with halothane anesthesia

32P-Labeled phospholipids with specific activities up to 400 mCi/mmole as well as [32P]CDP-choline were prepared by cultivation of mouse fibroblasts or mouse Ehrlich ascites cells in the presence of [32P]orthophosphate. The method was also used to prepare [methyl-3H]choline-labeled glycerophospholipids from [3H]choline. The yields and the specific activities of the phospholipids were significantly lower when preparations of ox white blood cells were used.     

An animal model of neuropathic pain: a review

Recent work has succeeded in producing models of painful peripheral neuropathies in laboratory animals. There is evidence that the animals experience both abnormal spontaneous pain and abnormal evoked pains (allodynia and hyperalgesia). Experimental analyses of these models have demonstrated potential pathophysiologic mechanisms in both the peripheral and central nervous systems; it is likely that the model neuropathic pain syndromes are due to several different mechanisms. One line of evidence suggests that these pain states gradually become centralized due to an excitotoxic effect on spinal cord dorsal horn inhibitory interneurons. The role of the sympathetic nervous system appears to vary, depending on the type of nerve injury and the temporal evolution of the syndrome. There is evidence indicating that the abnormality of cutaneous temperature regulation that often accompanies painful peripheral neuropathy is not necessarily due to the activity of sympathetic vasomotor efferents.     

Diaphragm replacement. An animal experiment study

OBJECTIVE: The study was designed to test the hypothesis that a dentifrice with fluoride at the same concentration (1000ppm) from two sources, ie NaF and NaMFP, would provide a greater treatment effect than one with NaMFP alone. BASIC RESEARCH DESIGN: A double blind clinical trial with random assignment of children to one of two groups was carried out for three years. The two trial groups were similar at the outset in respect to those variables which might otherwise have affected the outcome, including age and gender, with means per subject of 98.4 sound surfaces and 2.2 decayed and filled surfaces in each group initially. CLINICAL SETTING: Secondary schools in the Isle of Wight, UK, an area of diminished caries experience. PARTICIPANTS: One thousand six hundred and thirty-three children aged initially 10-12 years. INTERVENTIONS: A test dentifrice containing 500ppm NaF plus 500ppm NaMFP, and a standard active control product containing 1000ppm NaMFP. Products were used in the home. OUTCOME MEASURES: Increment of DF teeth and surfaces measured over 36 months. RESULTS: After three years, mean approximal surface increments were 3.6 new DFS in the control group and 3.1 in the test group, a difference 13 per cent (P < 0.05). Thirty-four per cent of the subjects were caries free at the outset. In the 1075 subjects with caries at the outset, the total mean increment on all surfaces was 7.2 new DFS in the control group and 6.4 new DFS in the test group, a difference of 11 per cent (P < 0.05). However, those subjects with initial caries had approximal surface increments of 4.8 new DFS in the control group and 4.0 new DFS in the test group, a difference of 16 per cent (P < 0.01). Included separately along with the conventional rubric were enamel white spots on which no differential treatment effect was observed. CONCLUSIONS: Under the conditions of this study, the regular use of a dentifrice containing 1000ppm fluoride from two sources provided a significantly greater treatment effect than one with fluoride from a single source.     

An animal model for cochlear microcirculatory disorders by photochemically initiated thrombosis

Making an ideal animal model of cochlear microcirculatory disorders is an important method in studying inner ear microcirculation. After intravenous injection of Rose bengal (30 mg/kg), the lateral wall of the cochlea of guinea pigs was illuminated with green light (wavelength: 550 +/- 20 nm). The Rose bengal photoactivatedly produces oxygen radicals and oxygen singlets, which subsequently damage the endotheliocytes to cause adhesion and aggregation of platelets in the small vessels. After the photo-illumination, cochlea blood flow reduced sharply, and CAP amplitude decreased in 10 min and disappeared completely in about 20-40 min. With prolongation of time, stria vascularis, Corti's organ and spiral ganglion cells showed further disintegration due to ischemia, which resembled the histopathological changes of the cochlea with microcirculatory disorders. Therefore, this animal model may be considered an ideal one for studying the mechanisms of hearing loss that was caused by microcirculatory disorders and also for evaluating the effects of drugs on microcirculation of damaged cochlea.     

An animal behavior model for studying the actions of LSD and related hallucinogens

Cats injected with LSD (d-lysergic acid diethylamide) exhibit a group of behaviors that appear to be specific to hallucinogenic drugs. Two of these behaviors, limb flick and abortive grooming, have an extremely low frequency of occurrence in normal cats, but often dominate the behavior of LSD-treated cats. The frequency of occurrence of this group of behaviors is related to the dose of LSD. The behavioral changes are long-lasting following a single injection of LSD, and exhibit tolerance following the repeated administration of LSD. They are not elicited by a variety of control drugs, but are elicited by other indole nucleus hallucinogens. Because the behavioral effects are specific, reliable, easy to score, and quantifiable, they represent an animal model that can be used in studies of the effects of LSD and related hallucinogens.     

Compensatory nicotine self-administration in rats during reduced access to nicotine: An animal model of smoking reduction.

The ability of smoking reduction (e.g., decreasing cigarettes per day) to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon. The goal of the current study was to develop an animal model of smoking reduction and to begin to examine potential behavioral and pharmacokinetic contributors to compensation. Rats trained for nicotine self-administration (NSA) in unlimited access sessions were exposed to a progressive decrease in duration of access to nicotine from 23-hr/day to 10-, 6-, and 2-hr/day. Following a return to 23 hr/day access and extinction, single-dose nicotine pharmacokinetic parameters were determined. Rats exhibited a reduction in total daily nicotine intake during reduced access to NSA, but decreases in nicotine intake were not proportional to decreases in access duration. Compensatory increases in hourly infusion rate were also observed when access was decreased. The magnitude of compensation differed considerably among animals. Early session infusion rate during baseline was significantly correlated, while nicotine clearance was moderately correlated, with 1 measure of compensation. Infusion rates were transiently increased compared to prereduction levels when unlimited access was restored, and this effect was greatest in animals that had exhibited the greatest levels of compensation. These findings indicate that rats exhibit compensatory increases in NSA during reduced access to nicotine, with substantial individual variability. This model may be useful for characterizing underlying factors and potential consequences of compensatory smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toward an animal model of Type A behavior.

Attempted to differentiate behaviors of Mongolian gerbils analogous to Type A (coronary-prone) and Type B (non-coronary-prone) human behavior. Preliminary classification of 20 Ss was based on performance on differential reinforcement of low rates 20-sec and 60-sec schedules. To retain their preliminary classification, Type A and Type B Ss were required to be dominant and subordinate, respectively, in matches with Ss of opposite behavioral classification. Ss that exhibited Type A timing won significantly more dominance matches than did Type B Ss. Incidence rates of Type A and Type B behavior in the 2 selectively bred generations were significantly greater than frequencies in the original stock. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hepatitis among plasma fractionation workers. An industry-wide study

An industry-wide survey of plasm fractionation facilities in the United States was conducted during 1973-74. Hepatitis was reported among the workers with varying degrees of plasma contact at all plant sites. For each of fourteen facilities in this investigation, field inspections disclosed: (1) numerous overt instances of employee-product contact: (2) inconsistent methodologic approaches at virtually all stages of the plasma fractionation process; (3) at low level of management and employee awareness regarding the potential bio-hazard identified; and (4) disparate examples of hepatitis surveillance and prophylaxis. Our data suggests that there is a high risk of hepatitis among plasma fractionation workers and, as such, much more attention needs to be focused on the reduction of health hazards within this industry.