Comparison of sympathetic sprouting in sensory ganglia in three animal models of neuropathic pain

Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after peripheral nerve injury. Therefore, one possible contributing factor of sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting in the DRG after peripheral nerve injury. The present study compared the extent of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in three rat neuropathic pain models: (1) the chronic constriction injury model (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the segmental spinal nerve ligation injury model (SSI). All three methods of peripheral nerve injury produced behavioral signs of ongoing and evoked pain with some differences in the magnitude of each pain component. The density of sympathetic fibers in the DRG was significantly higher at all examined postoperative times than controls in the SSI model, while it was somewhat higher than controls only at the last examined postoperative time (20 weeks) in the CCI and PSI models. Therefore, data suggest that, although sympathetic changes in the DRG may contribute to neuropathic pain syndromes in the SSI model, other mechanisms seem to be more important in the CCI and PSI models at early times following peripheral nerve injury.     

Anxiolytic effects of mecamylamine in two animal models of anxiety.

Clinical and preclinical evidence suggests that mecamylamine, a nicotinic receptor antagonist, may have anxiolytic properties. The purpose of this study was to further investigate the anxiolytic properties of mecamylamine in rats as measured by the Elevated Plus Maze and the Social Interaction models of anxiety and to determine if manipulation of the testing environment (either brightly lit or dimly lit conditions) influenced the results. Results indicate that mecamylamine had significant anxiolytic effects in both the Elevated Plus Maze and Social Interaction Tests and that these effects were dependent on dose administered and the level of anxiety produced under different testing conditions. If confirmed by further clinical research, nicotinic receptor antagonists like mecamylamine may represent a novel class of anxiolytics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Noninteractive effects of diazepam and amygdaloid lesions in two animal models of anxiety.

The role of the amygdala in mediating the anxiolytic effects of diazepam was examined in 2 models of rat anxiety. As in previous experiments (e.g., C. Pesold and D. Treit; see PA, Vol 80:4610; Treit et al; see PA, Vol 80:36896), amygdaloid lesions by themselves did not increase rats' exploration of the open arms of the elevated plus-maze or decrease rats' burying of an electrified probe in the shock-probe burying test. However, amygdaloid lesions did increase rats' shock-probe contacts. Diazepam (2 mg/kg) increased open-arm activity and decreased burying behavior to an equal extent in sham-lesioned and amygdala-lesioned rats and had no significant effect on the facilitation of probe contacts induced by amygdaloid lesions. These results suggest that many of the anxiolytic effects of benzodiazepines are not mediated by the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Third-party intervention: A field experiment comparing three different models.

A field experiment was conducted at a community mediation center to test the impact on behavior in mediation of three models of third-party intervention. Third parties and disputants were randomly assigned to one of three conditions: (a) straight mediation; (b) mediation/arbitration (same), or med/arb(same); or (c) mediation/arbitration (different), or med/arb(diff). These models differ in what happens if agreement between the disputants is not reached. In straight mediation, the hearing simply ends; in med/arb(same), the third party arbitrates; in med/arb(diff), a fourth party not present at the mediation hearing arbitrates. Results indicated that disputants in med/arb(same) engaged in more problem solving and were less hostile and competitive than were disputants in straight mediation, with med/arb(diff) intermediate on these dimensions. Third parties in med/arb(diff) were less involved throughout the session than were third parties in the other two conditions. Results are discussed in terms of motivational influences induced by the three conditions that have impact on tactics used by disputants and third parties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned effects of kindling three different sites in the hippocampal complex of the rat.

Rats received kindling stimulations to the perirhinal cortex (PRh), ventral hippocampus (VH), or dorsal hippocampus (DH) in 1 environment and an equivalent number of sham stimulations in a 2nd environment. The PRh-kindled rats displayed rapid kindling and a swift emergence of conditioned interictal defensiveness. In contrast, the VH- and DH-kindled rats displayed much slower kindling and slow or no conditioning, respectively. No effects of conditioning on the convulsions, comparable with those associated with amygdala kindling, were observed. These results establish the generality of some of the previously reported kindling-related conditioned effects, confirm the site specificity of some of these effects, and suggest that the convulsions, rather than the stimulations, function as the unconditioned stimuli for the conditioning of interictal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental animal models in cerebral ischemia

This paper describes the potential markers of cell death and connective tissue degradation which might serve as markers of periodontal disease activity. The first section deals with enzymes released by dead and degenerating cells. Firstly, it describes how these pass from the periodontal tissues into gingival crevicular fluid (GCF) and explains that these enzymes have been used as markers of cell death in medicine for several decades. It then discusses the main enzymes in this group, aspartate amino transferase (AST) and lactate dehydrogenase (LDH) and reviews those studies which have attempted to relate these enzymes to periodontal disease severity and activity. Secondly, it describes the potential markers of connective tissue degradation, fibronectin, hydroxyproline-containing peptides and glycosaminoglycans (GAGs) and explains how these are produced. Finally, it describes the only commercial test kit for markers in this group (GCF-AST).     

Comparison of the effects of the thrombin inhibitor r-hirudin in four animal models of neointima formation after arterial injury

Thrombin has been implicated as a contributing factor to restenosis after vessel reopening procedures. We compared the ability of the direct thrombin inhibitor recombinant (r-) hirudin to reduce neointimal growth in different animal models of arterial injury. Carotid arteries of rats, rabbits, and hypercholesterolemic minipigs were injured by withdrawal of an inflated balloon catheter. In addition, we used a double-lesion model in rabbits, which involved balloon angioplasty of a preexisting lesion induced by carotid denudation 4 weeks earlier. r-Hirudin was given in all four animal models as a short-term application (bolus of 1 mg/kg i.v. immediately before injury, followed by infusion of 1 mg.kg-1.h-1 for 2 hours, and an injection of 6 mg/kg SC). Additionally, we investigated the effects of prolonged treatment (intravenous infusion for 3 and 14 days) in rats. Inhibition of thrombin was monitored by determination of activated partial thromboplastin time, and histomorphometric analysis of the arteries was performed after 2 (rats) or 4 (rabbits and minipigs) weeks. In rabbits, short-term r-hirudin treatment reduced neointimal area by 59% (single-injury model, P = .05) and 44% (double-injury model, P = .02). In rats and minipigs no inhibition of neointimal growth was observed after short-term r-hirudin application. A 3- or 14-day infusion of r-hirudin in rats, however, resulted in 25% (P = .007) and 27% (P = .003) reductions in neointimal area, respectively. In conclusion, there is considerable interspecies variation in the time frame of susceptibility for reduction of neointimal growth by inhibition of thrombin after arterial injury. These results demonstrate the importance of testing potential antirestenotic treatments in an array of different animal models.     

Genetic dissection of obesity in polygenic animal models

In contrast to diseases caused by single-gene defects, many of the most common human maladies such as obesity, atherosclerosis, diabetes, and hypertension exhibit continuous phenotypic variation and a predominantly multifactorial and polygenic basis. Genes with roles in energy balance, nutrient partitioning, lipid and insulin metabolism, and a variety of behavioral traits are likely interacting with environmental stimuli to regulate obesity phenotypes. With the current proliferation of highly polymorphic genetic markers and the refinement of experimental approaches, it is now possible to screen thoroughly the genomes of model organisms for the individual genes or quantitative trait loci (QTL) that control measurable polygenic traits such as obesity. With the growing wealth of comparative mapping, it will be possible to predict the location of a homologous locus in the human after first mapping it in the mouse. Many experiments have been conducted in mice, rats, and pigs to estimate the number, location, and effect of QTL controlling obesity and related traits. This review describes the design and strategies of such studies and summarizes the results and their implications toward understanding the complex nature of obesity in humans.     

Aromatic hydroxylation in animal models of diabetes mellitus

Although the involvement of oxidative stress is well documented in the diabetic state, the individual active oxygen species generated have not been demonstrated in animal models of diabetes currently used. Since streptozotocin-induced diabetes mellitus in animals still serves as an animal model of diabetes mellitus, but streptozotocin induces diabetes and generates oxidative stress per se, we decided to study whether aromatic hydroxylation reflecting hydroxyl radical attack was found in three animal models of diabetes mellitus without streptozotocin induction or in streptozotocin-induced diabetes only. For this purpose, we compared lipid peroxidation, aromatic hydroxylation of phenylalanine, glycoxidation in genetically determined diabetic mouse strains db/db and kk, and the diabetic BB rat to these parameters in the streptozotocin-treated rat. Kidney malondialdehyde concentrations, reflecting lipid peroxidation, pentosidine, and Nepsilon-caboxymethyllysine concentrations, reflecting glycoxidation, were significantly elevated in all diabetic groups as compared to their nondiabetic mates. Aromatic hydroxylation was significantly elevated in the streptozotocin-induced diabetic state exclusively. We conclude that biochemical, pathophysiological, and treatment studies in the streptozotocin model of diabetes mellitus may be confounded by the presence of products, reactions, and tissue damage generated by aromatic hydroxylation reflecting hydroxyl radical attack. We suggest it is not the diabetic state but streptozotocin that generates the hydroxyl radical, as reflected by aromatic hydroxylation in this model.     

Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is not observed in three animal models

OBJECTIVE AND DESIGN: The effect of tenidap on the metabolism of arachidonic acid via the 5-lipoxygenase (5-LO) pathway was investigated in vitro and in vivo. MATERIALS AND TREATMENT: In vitro (cells). Arachidonic acid (AA) stimulated rat basophilic leukemia, (RBL) cells; A23817 activated neutrophils (human rat, and rabbit), macrophages (rat), and blood (human). In vitro (enzyme activity). RBL-cell homogenate; purified human recombinant 5-LO. In vivo: Rat (Sprague-Dawley) models in which peritoneal leukotriene products were measured after challenge with zymosan (3 animals per group), A23187 (11 animals per group), and immune complexes (3-5 animals per group), respectively. METHODS: 5-Hydroxyeicosatetraenoic acid (5-HETE) and dihydroxyeicosatetraenoic acids (diHETEs, including LTB4) were measured as radiolabeled products (derived from [14C]-AA) or by absorbance at 235 or 280 nm, respectively, after separation by HPLC. Radiolabeled 5-HPETE was measured by a radio-TLC analyser after separation by thin layer chromatography (TLC). Deacylation of membrane bound [14C]-AA was determined by measuring radiolabel released into the extracellular medium. 5-LO translocation from cytosol to membrane was assessed by western analysis. Rat peritoneal fluid was assayed for PGE, 6-keto-PGF1 alpha, LTE4 or LTB4 content by EIA and for TXB2 by RIA. RESULTS: Tenidap suppressed 5-LO mediated product production in cultured rat basophilic leukemia (RBL-1) cells from exogenously supplied AA, and in human and rat neutrophils, and rat peritoneal macrophages stimulated with A23187 (IC50, 5-15 microM). In addition, tenidap was less potent in inhibiting the release of radiolabeled AA from RBL-1 cells (IC50, 180 microM), suggesting that the decrease in 5-LO derived products could not be explained by an effect on cellular mobilization of AA (i.e., phospholipase). Tenidap blocked 5-hydroxyeicosatetraenoic acid (5-HETE) production by dissociated RBL-1 cell preparations (IC50, 7 microM), as well as by a 100000 x g supernatant of 5-LO/hydroperoxidase activity, suggesting a direct effect on the 5-LO enzyme itself. In addition, tenidap impaired 5-LO translocation from cytosol to its membrane-bound docking protein (FLAP) which occurs when human neutrophils are stimulated with calcium ionophore, indicating a second mechanism for inhibiting the 5-LO pathway. Surprisingly, tenidap did not block the binding of radiolabeled MK-0591, an indole ligand of FLAP, to neutrophil membranes. Although its ability to inhibit the cyclooxygenase pathway was readily observed in whole blood and in vivo, tenidap's 5-LO blockade could not be demonstrated by ionophore stimulated human blood, nor after oral dosing in rat models in which peritoneal leukotriene products were measured after challenge with three different stimuli. The presence of extracellular proteins greatly reduced the potency of tenidap as a 5-LO inhibitor in vitro, suggesting that protein binding is responsible for loss of activity in animal models. CONCLUSIONS: Tenidap inhibits 5-lipoxygenase activity in vitro both directly and indirectly by interfering with its translocation from cytosol to the membrane compartment in neutrophils. A potential mechanism for the latter effect is discussed with reference to tenidap's ability to lower intracellular pH. Tenidap did not inhibit 5-LO pathway activity in three animal models.     

Long-term effects of repeated maternal separation on three different latent inhibition paradigms

In the present study we investigated the effect of repeated maternal separation on postnatal days 12, 14, 16, and 18 for 6 h/day on Wistar rats on three latent inhibition (LI) paradigms: two-way active avoidance, conditioned emotional response (CER), and conditioned taste aversion (CTA). In addition, hyperactivity induced by d-amphetamine and stereotypies induced by apomorphine were evaluated. In all three LI experiments, the control animals showed only marginal LI, whereas the maternally separated animals showed enhanced LI (only males in CTA). In two-way active avoidance within the nonpreexposed condition maternally separated animals showed improved acquisition of avoidance learning compared with the control animals. Sensitivity in response to amphetamine and apomorphine was not altered by the maternal separation procedure. Thus, maternal separation in this study, contrary to previous reports, but in line with results obtained following early handling before weaning, led to enhancement of the LI phenomenon as assessed in each of the three procedures. As our maternal separation procedure (6 h on days 12, 14, 16, and 18) led to behavioral outcomes that differed from those reported by Ellenbroek and Cools (24 h on day 10), it is suggested that maternal separation regimens that are dissimilar may lead to different and sometimes opposite behavioral effects.     

Anxiogenic-like consequences in animal models of complex partial seizures

Extracellular adenosine triphosphate (ATP) plays an important role in the regulation of endothelial function. However, its receptors and their signal-transduction pathways in major cerebral arterial endothelial cells are largely unknown. This study was undertaken functionally to classify the P2 purinoceptors in cultured bovine middle cerebral artery endothelial cells by using [Ca2+]i microfluorimetry. The rank order of potency to increase [Ca2+]i was 2-methylthio-ATP approximately ATP approximately uridine triphosphate (UTP) > adenosine diphosphate (ADP) > adenosine monophosphate (AMP) > alpha,beta-methylene-ATP > adenosine, suggesting that the effect was mediated by both P2y and P2u receptors. ATP, 2-methylthio-ATP, and UTP mobilized Ca2+ from intracellular stores and triggered Ca2+ entry. The effects of ATP, 2-methylthio-ATP, and UTP were reduced by phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), but only the effects of ATP and UTP were attenuated by pertussis toxin, indicating that P2y and P2u receptors may activate the same effector mechanisms by coupling to different G proteins. The [Ca2+]i entry caused by UTP was significantly reduced by the receptor-regulated Ca2+ channel blocker SK&F 96365, by P-450 inhibitor econazole and by inorganic Ca2+ entry blocker lanthanum. P2-receptor antagonists suramin, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), and reactive blue 2 reduced the effects of ATP and 2-methylthio-ATP, but not those of UTP, in a concentration-dependent manner. These studies suggest a coexistence of P2y and P2u receptors in cultured bovine middle cerebral artery endothelial cells.     

Lessons from animal models of atrial arrhythmias

This article presents selected lessons from experimental studies of atrial fibrillation and atrial flutter that pertain to the mechanisms and predisposing factors for flutter and fibrillation and approaches to treatment by antiarrhythmic drugs. Experimental studies also provide lessons for the effects of ablation and surgical lesions on prevention or facilitation of atrial fibrillation and flutter.     

Development of animal models for the chronobiotics of melatonin analogs

We reviewed the records of patients admitted to our centre with the diagnosis of isolated tricuspid valve infective endocarditis and analysed the clinical presentation, etiopathogenic agent, echocardiographic features and therapeutic approach, namely the indication for cardiac surgery. Between 1988 and 1996, 11 cases of confirmed tricuspid valve endocarditis were identified, corresponding to 5% of the cases of endocarditis admitted to our centre in the same period. A predisposing factor was found in ten of the patients, half of them intravenous drug addicts and Staphylococcus aureus was the most frequent agent isolated. Fever and pleuro-pulmonary manifestations were predominant clinical features. Transthoracic echocardiography had a crucial role in the diagnosis and transesophageal echocardiography was important to characterize vegetations. Four patients underwent cardiac surgery, for persistent infection. In two cases, excision of the vegetations and ring annuloplasty was performed. In two patients not addicted to drugs, the tricuspid valve was replaced with a bioprosthesis, since the extension of the damage to the valve did not allow repair. One patient, with early endocarditis of a tricuspid bioprosthesis died before surgery was attempted.     

Endogenous nitric oxide in the airways of different animal species

BACKGROUND: High amounts of endogenous nitric oxide (NO) have been demonstrated in the human upper airway, but the role of nasal NO is still unclear. The present study aims to describe nasal NO excretion in different animal species with special living conditions or anatomy. METHODS: Domestic animals (horse, cow, pig, sheep, dog, cat) and zoo-animals (Rhesus monkey, chimpanzee, gorilla, elephant, fur seal, alpaca, yak, dolphin, camel, capybara, bear, tiger, wolf, giraffe, alligator, Harris' hawk, kangaroo) were studied awake, resting or anaesthetised. NO concentrations were measured by chemiluminescence using different analysers and techniques, including measurements on mixed exhaled air, during continuous or intermittent gas sampling, and on single breaths. RESULTS: Rhesus monkeys (number of individuals N = 5) and pigs (N = 2) were compared and displayed quite different excretion patterns. Allowing NO to accumulate in the nose during timed occlusions yielded peak concentrations in monkeys of 0.46 +/- 0.07 parts per million (ppm, mean +/- SEM), 0.59 +/- 0.08 ppm, 0.70 +/- 0.08 ppm and 1.02 +/- 0.05 ppm NO after 15, 30, 60 and 120 s of occlusion. In pigs, 0.012-0.021 ppm NO were recorded, independent of occlusion time. The chimpanzee was similar to the Rhesus monkey and the highest NO value, 2.9 ppm, was recorded after 4-5 min of occlusion. In single breaths from 3 elephants 0.031-0.082 ppm, from 1 gorilla 0.029 ppm, and from 1 chimpanzee 0.069 +/- 0.003 ppm NO (8 observations) were recorded. CONCLUSIONS: We found considerable species difference in nasal NO excretion with pronounced amounts only in primates and elephants. The physiological implications of these findings remain to be defined.     

Transgenic animal models for the functional analysis of vasoactive peptides

The interplay of vasoactive peptide systems is an essential determinant of blood pressure regulation in mammals. While the endothelin and the renin-angiotensin systems raise blood pressure by inducing vasoconstriction and sodium retention, the kallikrein-kinin and the natriuretic-peptide systems reduce arterial pressure by eliciting vasodilatation and natriuresis. Transgenic technology has proven to be very useful for the functional analysis of vasoactive peptide systems. As an outstanding example, transgenic rats overexpressing the mouse Ren-2 renin gene in several tissues become extremely hypertensive. Several other transgenic rat and mouse strains with genetic modifications of components of the renin-angiotensin system have been developed in the past decade. Moreover, in recent years gene-targeting technology was employed to produce mouse strains lacking these proteins. The established animal models as well as the main insights gained by their analysis are summarized in this review.     

Lipid peroxidation and lysosomal integrity in different inflammatory models in rats: the effects of indomethacin and naftazone

The authors tried to establish quantitative and qualitative acoustic parameters of a good voice, suitable for future voice professionals. In their work they used long-time average spectrum analysis (LTAS) and three-dimensional analysis of periodicity (3D-PAN). They consider the regression straight line of formant regions and the parameters offered by 3D-PAN--jitter first of all--as the main acoustic parameters for the evaluation of voice quality and draw attention to the fact that acoustic parameters represent only one part of the evaluation of voice quality.     

Interactive effects of three structurally different polychlorinated biphenyls in a rat liver tumor promotion bioassay

PURPOSE: Our goal was to validate linear and nonlinear intersubject image registration using an automated method (AIR 3.0) based on voxel intensity. METHOD: PET and MRI data from 22 normal subjects were registered to corresponding averaged PET or MRI brain atlases using several specific linear and nonlinear spatial transformation models with an automated algorithm. Validation was based on anatomically defined landmarks. RESULTS: Automated registration produced results that were superior to a manual nine parameter variant of the Talairach registration method. Increasing the degrees of freedom in the spatial transformation model improved the accuracy of automated intersubject registration. CONCLUSION: Linear or nonlinear automated intersubject registration based on voxel intensities is computationally practical and produces more accurate alignment of homologous landmarks than manual nine parameter Talairach registration. Nonlinear models provide better registration than linear models but are slower.