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Development of an experimental model of liver cirrhosis in rabbits.

1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) by intragastric administration of CCl4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dose of CCl4 was 20 microg and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals did not gain weight compared with controls (P < 0.05). A significant reduction of ICG clearance was observed in CCl4-treated rabbits compared with controls (P < 0.05). The AST, ALT, bilirubin and gamma-GGT levels were elevated in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.

Animals↗

Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats.

BACKGROUND AND PURPOSE: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis. EXPERIMENTAL APPROACH: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature. KEY RESULTS: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression). CONCLUSIONS AND IMPLICATIONS: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.

Animals↗

Functional morphology of the adrenocortical glomerular zone by incomplete ligation of bilateral ureters of rats. An experimental model for secondary aldosteronism.

We studied the adrenal cortex, particularly the glomerular zone of an experimental model for secondary aldosteronism produced in rats by incomplete ligation of both ureters. The experimental animals developed characteristic manifestations of the disease such as ascites and high serum potassium, PRA, and aldosterone content in the adrenal tissue. Microscopically, the width of the glomerular zone was markedly increased and this was related to hypertrophy of the cells of the glomerular zone. Lipid droplets in these cells were decreased. The enzymic activity of 3 beta-HSD showed a moderate increase in the transitional zone and a slight increase in the glomerular zone. Ultrastructurally, well-developed mitochondria and SER were seen in swollen cytoplasm and numerous microvillous projections were noted in the plasma membrane. These results suggest that the adrenal cortical cells in the glomerular zone are stimulated by high concentrations of serum potassium and renin-angiotensin.

Adrenal Cortex↗

An experimental model for meningeal leukemia in rats (L5222). Effect of treatment with BCNU and cyclophosphamide.

An experimental model of meningeal leukemia in rats is developed by intracerebral (IC) inoculation of leukemic cells from the transplantable acute leukemia L5222. The L5222 proliferates exponentially in the central nervous system (CNS) and the disease becomes systemic 2 days following IC inoculation. Chemotherapeutic studies with BCNU and cyclophosphamide yielded cures in a high percentage of cases when treatment began at an early stage of meningeal leukemia. When treatment was started at the advanced stage, only BCNU showed a large number of cures. However, cyclophosphamide resulted in a marked increase of life-span. The activity of cyclophosphamide against meningeal leukemia, which is in contrast to the results obtained by Skipper et. al. (1961) in the L1210 mouse leukemia, suggests that cyclophosphamide crosses in part the blood--brain barrier in a rat bearing meningeal leukemia. After subcutaneous inoculation, BCNU and cyclophosphamide showed the same rate of cures.

Animals↗

Experimental models of stress and wound healing.

Experimental animal models have been used to examine stress-induced interactions among the nervous, endocrine, and immune systems. Generally, the response to stress results in a body-wide set of physiologic adaptations, mediated through the activation of neuroendocrine pathways that intersect and modulate inflammatory and immune responses. These interacting responses modulate diverse physiological processes including the initiation of tissue repair and wound healing. Two different stressors were used to activate neuroendocrine responses to study their impact on wound healing: restraint (RST) and social disruption (SDR). Previous studies showed that both stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, resulting in elevated plasma levels of the corticosterone (cort) response and modulation of pro-inflammatory cytokine response. To test the effects of stress-induced HPA activation on inflammatory responses and wound healing, a 3.5-mm cutaneous punch biopsy wound was placed on the dorsal surface of control and stressed (RST or SDR) C57BL/6 male mice and the kinetics of wound healing were studied over 10 days. RST slowed wound healing in inbred C57BL/6 mice, whereas the wounds on SDR mice healed in a fashion similar to the non-stressed, home cage controls.

Analysis of Variance↗

Experimental models of IgA nephropathy.

Several different experimental animal models of IgA nephropathy contribute to our understanding of the clinical disease. These models collectively indicate that IgA immune complexes can deposit in glomeruli and elicit the characteristics of IgA nephropathy; they also establish the potential for an IgA immune response to generate, in the face of antigen exposure, IgA-containing immune complexes. Defective immunoregulation, mononuclear phagocyte function, and the role of antigen and complement on glomerular function emerge from the animal studies as issues ripe for clinical investigation.

Animals↗

Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain.

A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.

Adult↗

Experimental models of hepatic fibrosis in the rat.

The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation.

Animals↗

Development of an experimental model of Microsporum canis infection in cats.

An experimental infection model was developed for reliable induction of Microsporum canis skin infections in cats, using a defined number of macroconidia harvested from the fungus in culture. The strain of M. canis used produced highly fluorescent hairs under ultraviolet illumination. Kittens 8 to 9 weeks of age (n = 6) received 10(5) macroconidia applied topically to a closely-shaved area of skin. Sites were dressed with an occlusive bandage for 3 days, then grooming was restricted for an additional 4 weeks. Lesions were first observed 2 weeks after inoculation, enlarged over the following 6 to 8 weeks, then decreased in size and appeared healed at 12 to 14 weeks after inoculation. Cats often developed satellite lesions on the face, ears, or other body regions. The experimental infections strongly resembled moderately severe cases of naturally-occurring feline dermatophytosis in clinical patients. This experimental infection model will be useful for evaluation of topical and systemic treatments for feline M. canis infection.

Animals↗

Experimental model of posttraumatic syringomyelia: the role of adhesive arachnoiditis in syrinx formation.

An experimental model was devised to elucidate the role of spinal blockade in posttraumatic syringomyelia. Thirty-eight Japanese White rabbits, each weighing about 3 kg, were used in this study. The animals were divided into four groups: in Group 1, eight animals received traumatic injury only; in Group 2, 12 animals received traumatic injury following injection of 100 mg kaolin suspended in 1 cc normal saline solution into the subarachnoid space at the site of trauma; in Group 3, nine animals received traumatic injury following injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space at the site of trauma; and in Group 4, nine animals without traumatic injury received an injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space. The subjective criteria for syrinx formation were the presence of a definite round cyst having a smooth margin and an upper or lower extension of more than 2 cm from the injured site. Syrinx formation was seen in 12.5% (one of eight rabbits) in Group 1, 41.7% (five of 12 animals) in Group 2, 55.5% (five of nine rabbits) in Group 3 and 0% (none of nine animals) in Group 4 (p < 0.05). There was a tendency for the combined trauma/kaolin injection groups to be more prone to develop a syrinx. In the kaolin injection only group (Group 4), no animal showed a definite cyst or an extending cavity during the experimental period. The results suggest that kaolin enhances the extension of multiple small cavities that have already formed at the time of initial injury. The difference between the frequency of syrinx formation and the time of survival was statistically significant well beyond the 0.05% level. The overall difference, relating to the frequency of syrinx development, group, and duration of survival, was also statistically significant. In summary, subarachnoid block secondary to adhesive arachnoiditis is important in initiating the extension of the syringomyelia cavity.

Animals↗

Experimental models of head injury.

Experimental research in studies of head injury may be directed along theoretical, mechanical and experimental animal and clinical lines. The parameter of the results compared may thus be the mechanics of skull or the skull contents, pathophysiological changes or pathomorphological lesions. Due to the variation of the daily accidents and resulting injuries each series of problems must be studied with suitable technique. Often the various types of studies determine the possibility of interpreting the results for clinical analysis and prevention. However, this is often possible if all experimental conditions and parameters studied are precisely defined. Movements, deformations of skull and the intracranial contents, results from rotational and angular acceleration and velocities as well as the direction and the site of impact in the human being must always be considered.

Animals↗

Intracranial pressure in a modified experimental model of closed head injury.

Intracranial pressure (ICP) was studied in a modified experimental model of closed head injury, in which the dynamic process of impact versus impulse loading was separately controlled. In this model, mortality of Wistar rats was considerably higher as compared to Sprague-Dawley rats subjected to similar traumatic conditions. Therefore Sprague-Dawley rats were used for all further experiments. Twenty-four rats, divided into 4 groups, underwent either sham or gradually increasing impact-acceleration trauma. Four hours after closed head injury, ICP measurements showed a significant correlation between the severity of the traumatic challenge and the resultant pressure rise (r2 = 0.731; p < 0.001). At the moment of impact there was a momentary blood pressure peak immediately followed by a transient period of hypotension. ICP measurements following directly to an impact-acceleration trauma, revealed an abrupt rise in ICP reaching pathological levels within 5 minutes. In conclusion, this modified model of closed head injury produces a predictable and reproducible pathologic ICP in Sprague-Dawley rats.

Animals↗

An experimental model of communicating hydrocephalus in C57 black mouse.

The authors report a new experimental model for the study of hydrocephalus. Hydrocephalus was produced in C57 black mouse by transplanting human glioma cultured cells. 20% of the animals developed hydrocephalus while the incidence of spontaneous hydrocephalus is only 1%. The transplanted cells disappeared within 72 hours. The mouse developed progressive hydrocephalus. There was no evidence of blockage of CSF pathways. The only abnormal microscopic finding was a scattered collection of lymphoid cells in some of the animals, which may be a hypersensitivity reaction to the cells. A similarly hypersensitive reaction to the foreign maternal protein which may enter the foetal circulation is suggested as the cause of hydrocephalus in some of the cases of congenital hydrocephalus.

Animals↗

The mucosa of the rabbit vagina: a proposed experimental model for correlated morphofunctional studies in humans.

In order to suggest a valid experimental model for correlated studies regarding the complex phenomena of reproductive biology in humans, light (LM), transmission (TEM) and scanning electron microscopic (SEM) observations were carried out on vaginae of sexually mature New-Zealand albino rabbits, both in estrus and at 5 h after mating. To avoid artifacts depending upon the operative times for specimen removal and, in particular, to well visualize the inner surface of this organ, vaginal irrigation with fixative was performed prior to the surgical removal. Our data demonstrate that the upper 2/3 of the vaginal duct form a kind of 'cervico-vaginal canal' which shares many histological features with the human endocervix. In fact, this portion is lined within by a monostratified epithelium provided with tall microvillous and ciliated cells and often invaginated in crypts. After mating, the microvillous cells showed evidence of secretory activity, exhibiting dome-like luminal surfaces. Secretory droplets often contacted cilia and spermatozoa present in the mucosal furrows and crypts. Because of these singular features and the morphofunctional interactions between vaginal epithelium and male gametes, we believe the rabbit to be a helpful model for comparative biology in humans, concerning sperm capacitation and the general reactivity of the female genital tract during the reproductive cycle.

Animals↗

[A new experimental model of cecal amebiasis in rats].

The young rat was used as an experimental model of caecal amebiasis by implanting, without injury of the caecum, a suspension of E. histolytica trophozoites gnotoxenic strain Rahman of high virulence. The degree of pathogenicity is demonstrated by the macroscopic aspect of caecum, by the density of trophozoites and by an anatomopathologic examination. As a correlation exits between all these macroscopic parameters and histology, a degree of illness is fixed which include several macro- and microscopic criteria. This model enables to observe the different phases of cicatrization and of recovering of young rats and so to appreciate the activity of antiamebic agents.

Amebiasis↗

A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage.

A new experimental model of subarachnoid hemorrhage (SAH) in rats is described. A needle was stereotaxically placed in the prechiasmatic cistern and 300, 250 or 200 microl of blood was injected manually, keeping the intracranial pressure (ICP) at the mean arterial blood pressure (MABP) level. An acceptable mortality was observed only after injection of 200 microl of blood. In this group, MABP and ICP increased immediately after SAH, but soon approached baseline levels. The subarachnoid blood was mainly distributed in the basal cisternal system and its estimated volume was about 95% of the amount injected. This new model resembles clinical SAH, is very reproducible, easy to use and seems to be a suitable model for studies of the pathophysiology of SAH.

Animals↗

An experimental model of scalp expansion: a method of optimizing flap size and shape.

An experimental model has been developed for testing and comparing the placement and characteristics of expanders for soft-tissue advancement. Expanders are fixed to model heads and covered with a stockinet sleeve, and the sleeve is impregnated with prevulcanized latex. The resulting stockinet-latex has many of the physical properties of skin and can be manipulated to ensure optimal covering and suture length prior to surgery. The system is rapid and reliable. Several types of scalp flaps were tested using the model. The models can be used in teaching and prior to surgery. Their use ensures an à la carte expansion that minimizes the risk of expansion failure.

Humans↗

Wound healing and formation of granulation tissue in normal and defibrinogenated rabbits. An experimental model and histological study.

The aim of this investigation was to develop an experimental model for studies on the significance of fibrin deposition for wound healing. Systemic defirbinogenation with Arvin was used to achieve abnormal fibrin deposition in subcutaneously implanted cellulose sponges. The formation of granulation tissue in the sponges was studied histologically. Arvin injections resulted in a rapid decrease in plasma fibrinogen concentration with a concomittant rise in fibrin-degradation products. No change in FXIIIa activity was seen. During defibrinogenation an abnormal fibrin deposition was found in the sponges. The fibrin strands appeared irregular and disrupted. The number of fibroblasts and collagen fibrils was reduced in granulation tissue formed during defibrinogenation. The model used seems to allow controlled studies on the significance of fibrin deposition for wound healing. Defibrinogenation was found to influence granulation tissue formation.

Animals↗