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Fasciocutaneous flaps: an experimental model in the pig.

No experimental studies have substantiated the claim that fasciocutaneous flaps are superior to skin flaps. Using fasciocutaneous flaps designed in the pig, both flap survival and blood flow were assessed. The forelimb and hindlimb fasciocutaneous flaps survived to 8.2 +/- 0.3 cm and 7.9 +/- 0.3 cm, respectively, compared with 7.3 +/- 0.3 cm and 6.7 +/- 0.3 cm for the comparable cutaneous flaps, a statistically significant finding (p less than 0.01). Random fasciocutaneous flaps survive 12 to 18 percent longer than skin flaps. Using the radioactive microsphere technique, blood flow was measured after flap elevation, and flap survival was estimated using fluorescein. Again, a significant difference in flap survival was found, but there was no significant difference in measured blood flow. This can be explained by the relatively large interval between blood flow measurements (2 cm) compared with the observed difference in survival length (1.0 +/- 0.3 cm).

Animals↗

[Role of nitric oxide in alterations of the systemic and splanchnic hemodynamics in a experimental model of portal hypertension].

Recent experimental studies have suggested that an increase in the synthesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to portal hypertension. The present study was addressed to investigate the effects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by partial portal vein ligation. Intravenous infusion of L-NNA (50 ug/kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increase in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (300 mg/Kg, i.v.) prevented the hemodynamic changes induced by L-NNA. Similar values of endotoxin levels were detected in both groups of animals. In the control group, L-NNA caused a mild but significant increase of mean arterial pressure; no significant changes on the other hemodynamic parameters were observed. These results suggest that an increase in endogenous synthesis of nitric oxide may play an important role in hemodynamic disturbances associated with chronic portal hypertension.

Animals↗

Pathogenic in vitro studies of pemphigus vulgaris. I. Experimental model of pemphigus vulgaris in cultures in diffusion chambers.

Normal human skin, cultivated in diffusion chambers with biological membranes in the presence of serum from pemphigus vulgaris patient in the culture, developed all microscopic signs of an acantholytic process. An experimental model of pemphigus was thus created for the first time in our country and proposed by the authors as suitable basis for further studies on the disease pathogenesis and treatment.

Culture Techniques↗

Experimental models of acute pancreatitis.

Acute pancreatitis remains a disease of uncertain pathogenesis and nonspecific therapy. Because of the practical problems plaguing investigation of pancreatitis in man, investigators have developed various experimental animal models of pancreatitis in order to develop rationale concepts regarding pathogenesis and therapy. Despite numerous investigations over the past century, the events involved in the initiation and progression of pancreatitis remain obscure. Indeed, identification of the cellular mechanisms responsible for the initiation of this disease may allow for significant advances in therapy. Previous studies have largely focused on the mechanism of pancreatitis at the organ level. It is now apparent that the early initiating events in acute pancreatitis probably occur at a membrane or intracellular level. The resolution of the cellular events which underlie the development of pancreatitis in combination with the introduction of new therapeutic agents may enable a rational and safe protocol to be developed for the support of patients with pancreatitis. In this review different experimental models of acute pancreatitis are discussed. Emphasis is placed on the relevance of various models to clinical pancreatitis.

Acute Disease↗

Endoneurial fluid pressure in experimental models of diabetic neuropathy.

The sorbitol pathway has been suggested as a biochemical mechanism for peripheral neuropathy in diabetes, due to accumulation of osmotically active polyols which cause endoneurial edema. The purpose of this study was to compare endoneurial fluid pressure (EFP) in the peripheral nerves of rats in three experimental models: streptozotocin diabetes, galactose neuropathy, and sucrose intoxication. Endoneurial fluid pressure was measured in 27 diabetic rats at intervals of 4 to 51 weeks after inoculation with streptozotocin and in ten control rats. Elevated fluid pressure was observed in only two diabetic animals, and there was no significant difference in mean EFP between test animals and controls. By contrast, elevated EFP was found in 9 of 11 rats who received a 68% sucrose diet for 48-51 weeks. The mean EFP in these animals was approximately twice normal, and sucrose intoxication thus appears to be a more effective model than streptozotocin diabetes for nerve edema associated with the sorbitol pathway.

Animals↗

Cancer cachexia: from experimental models to patient management.

Cachexia is frequently associated with advanced or terminal cancer states, but it can also develop early during the course of neoplastic disease. This syndrome, which is characterized by body weight loss and negative nitrogen balance, significantly affects patient survival and quality of life. Studies on experimental models have shown that a complex interplay of different factors, such as anorexia, classical hormones, cytokines and other less well defined factors, concur in causing tissue wasting. On the basis of these results, it has been possible to prevent the onset of experimental cachexia by targeting therapeutic interventions at the underlying metabolic perturbations. Anticytokine treatments, either acting centrally or peripherally, have received particular attention, and are currently reaching the stage of clinical trials.

Animals↗

[The adrenergic beta system in an experimental model of heart failure].

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.

Adenylyl Cyclases↗

Experimental models for studies on transportation of antibiotics to extravasal compartments.

A short review is presented illustrating different methods employed to determine the antibiotic concentration in different tissues in man and the limitation to perform thorough pharmacokinetic studies. The most often used experimental models (different tissue cage models the fibrin clot, skin blisters, skin windows, skin chambers) applied in animal and man for studies of antibiotics are presented as well as a discussion concerning their relevance to the clinical situation.

Animals↗

An experimental model system for leishmaniasis. Effects of porphyrin-compounds and menadione on Leishmania parasites engulfed by cultured macrophages.

In order to facilitate studies on the effects of chemotherapeutic agents on the host-parasite interactions in leishmaniasis, we have developed an experimental model for infecting human monocyte-derived- and mouse peritoneal macrophages in culture with recently-isolated Leishmania donovani promastigots (LDP). The chemotherapeutic agents studied were protoporphyrin, hematoporphyrin, menadione, and combinations of hematoporphyrin plus menadione. Since the Leishmania donovani amastigotes survived poorly in mouse macrophages and protoporphyrin was quite toxic to the latter, our investigations were focused on the effects of hematoporphyrin and menadione on amastigotes engulfed by human macrophages. Treatment of Leishmania donovani amastigotes-infested human macrophages with either 50 microM hematoporphyrin or 10 microM menadione did not influence significantly the survival of either Leishmania donovani amastigotes or the macrophages themselves. Larger individual doses of hematoporphyrin and menadione were toxic to both parasites and macrophages. The combination of 50 microM hematoporphyrin and 10 microM menadione, however, caused the destruction of the parasites without affecting the host macrophage. The enhanced deleterious effect from combined low doses of hematoporphyrin and menadione is discussed in terms of the production of reactive oxygen species, such as superoxide anion radical and hydrogen peroxide, originating from cellular redox cycling of menadione, and followed by decomposition of the formed hydrogen peroxide by hematoporphyrin to produce the more reactive hydroxyl radical.

Animals↗

Can monocortical miniplates provide bony compression?. An experimental model.

Some maxillofacial surgeons advocate that screws in monocortical plate systems be placed eccentrically in an attempt to provide compression between bony ends. We sought to quantify the degree of displacement and compressive forces made possible by such eccentric placement in an experimental model using five miniplates and Perspex blocks to simulate mandibular fractures. The maximum displacement obtained was 0.67 mm and the maximal compressive force 5.2N (SEM=0.9, range=2.7-7.1). This demonstrates that eccentric placement of screws can achieve some compression and displacement at the fracture interface and that the forces obtained are close to those predictable from the dimensions of the burr, screw, and miniplate.

Bone Plates↗

Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection.

Bacteraemia and subsequent sepsis is one possible complication of Clostridium difficile infection. The aim of this study was to examine a correlation between bacterial translocation with morphological changes of intestinal mucosa and shifts of intestinal microflora in experimental models of C. difficile infection. A mouse model was used to study post-antibiotic shifts and mild C. difficile infection, and hamsters were used to study fatal enterocolitis. The influence of pro- and pre-biotics (lactobacilli and xylitol) were also studied in the hamster model. The quantitative composition of luminal and mucosal microflora was evaluated in different intestinal loci, inflammatory changes of mucosa were estimated in histological sections and bacterial translocation was detected in samples from blood, liver, spleen and mesenteric lymph nodes. In cases of mild C. difficile infection, the extent of disturbance of intestinal microflora appeared to be a more important promoting factor in translocation than inflammatory activity in the mucosa. Translocation was frequent in fatal enterocolitis, with facultative species predominating in the intestinal mucosa and also C. difficile in some cases. The combination of lactobacilli and xylitol had some protective effect against C. difficile infection in these models.

Ampicillin↗

Influence of iron on Corynebacterium renale-induced pyelonephritis in a rat experimental model.

Growth of Corynebacterium renale in vitro on low-iron medium (1.34 micron) was only slightly less than that on high-iron media (7.16 and 9.85 micron). However, studies on C. renale-induced pyelonephritis using the rat as an experimental model revealed that C. renale cultivated in high-iron media was capable of producing pyelonephritis, but when grown on low-iron medium, these bacteria were noninfective. This apparent avirulence of the bacteria cultivated on low levels of iron could be reversed by injecting the rats intramuscularly with ferric ammonium citrate.

Animals↗

The cryofixation of isolated rat gastric mucosa provides new insights into the functional transformation of gastric parietal cells: an in vitro experimental model study.

Cryofixation is currently accepted as the best initial fixation step to preserve not only the fine structure but also the antigenicity of biological samples. To elucidate the functional transformation of gastric parietal cells, we have newly developed an in vitro experimental model, named the isolated gastric mucosa. In this study, acid secretion of the parietal cell was stimulated with histamine or inhibited with cimetidine, and the samples were cryofixed by plunge freezing for light microscopy or high-pressure freezing for electron microscopy. As a result, the organization of glandular cells was well-preserved and quite similar to freshly excised rat gastric mucosa for at least 2 h after isolation. Immunohistochemistry of H+/K+-ATPase demonstrated a translocation of H+/K+-ATPase from the cytoplasm to the apical membrane associated with histamine-stimulation. In cimetidine-treated mucosa, most of the parietal cells were morphologically in the resting state, showing numerous tubulovesicles in their cytoplasm. In contrast, histamine-stimulated parietal cells exhibited well-developed intracellular canaliculi lined with long microvilli. To the best of our knowledge, the present study is first to demonstrate an electron micrograph that strongly suggests a membrane fusion between the tubulovescile and the apical membrane. Moreover, a stimulation-associated translocation of ezrin was clearly shown from the cytoplasm to the apical region, corresponding to apical microvilli development in the isolated gastric mucosa model. We here describe the preparation of the isolated rat gastric mucosa model, which provides new insights into the functional transformation of parietal cells by the application of cryotechniques.

Animals↗

Antiinflammatory effect of flavonoids in the natural juice from Aronia melanocarpa, rutin and rutin-magnesium complex on an experimental model of inflammation induced by histamine and serotonin.

The antiinflammatory effects of the anthocyane flavonoids in the natural juice from Aronia melanocarpa and of rutin-magnesium complex, the water-soluble derivative of rutin were studied in comparison with rutin. Two experimental models of inflammation were used. Inflammation of rat hind paw was induced either by 0.5% solution of histamine or by 0.01% solution of serotonin. The swelling of the rat paw was measured oncometrically by a pletismometer. The results showed that the anthocyane flavonoids from the natural juice of Aronia melanocarpa exerted more pronounced effects as compared to rutin in both models of inflammation. The rutin-magnesium complex did not exhibit any antiinflammatory activity against histamine-induced inflammation. Its effects against serotonin-induced inflammation were comparable to those of rutin.

Animals↗

Experimental models of coronary artery restenosis.

The study of potentially effective drug therapies and mechanical devices for the prevention of restenosis after percutaneous coronary revascularization has relied heavily on the use of experimental animal models. To date, greater than 50 experimental studies have been reported and have suggested that at least nine different classes of pharmacologic agents inhibit the intimal proliferative response to arterial injury. However, no pharmacologic intervention has yet been shown to reproducibly reduce the incidence of restenosis after coronary balloon angioplasty in humans. To identify the reasons for the apparent nonspecificity of the animal models and to determine which model should most reliably predict the efficacy of individual therapies in humans, the distinguishing characteristics of the experimental models were compared. Particular attention was paid to the size and morphologic structure of the treated artery, the susceptibility of the species to spontaneous and diet-induced arterial disease, the nature of the stimulus to intimal proliferation and several practical and logistic considerations. Finally, the reported efficacies of specific drug therapies in the respective animal models and in humans were compared. This review suggests that significant interspecies and occasionally intraspecies differences do exist among the respective animal models, particularly in the extent and composition of the neointimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Experimental model of chronic osteomyelitis caused by Leishmania (L) amazonensis.

Experimental animal models have been used for the study of the physiopathogenesis of leishmaniasis, on some occasions with success, while in other situations such as bone alterations that accompany tegumentary leishmaniasis, especially in diffuse cutaneous form (DCL), the mechanisms are still unknown. In the present study, we determined these alterations in an animal model susceptible to Leishmania (L) amazonensis. Amastigotes of L. (L) amazonensis isolated from patients with diffuse cutaneous leishmaniasis (DCL) were inoculated into the hind paws of eight BALB/c mice, macroscopic and histopathological aspects were analyzed. After 90 and 120 days of evolution, histopathological analysis demonstrated a mononuclear cell infiltrate rich in plasma cells and intense parasitism of intra- and extra-medullary macrophages, with areas of bone necrosis and discrete involvement of cartilaginous tissue. The results show that the inflammatory process developed during L. (L) amazonensis infection might cause bone tissue destruction and secondarily affect the joints.

Animals↗

[Animal experimental model of lung contusion].

Introduction and discussion of an experimental animal model to the representation of an isolated lung contusion in rats. The damage is realized by means of pressure waves. There can be observed distinct lung contusions - even unilateral - without chest wall lesions or extrathoracal injuries. One can also recognize temporal lapses of different intensity of the trauma. The model appears suitable to the presentation of a possible independent pathogenesis of the lung contusion.

Animals↗

An experimental model of cerebral microischemia in rabbits.

Multiinfarct dementia is the second most common form of dementia in the elderly. An animal model of microischemia may provide information about the pathophysiology relevant when searching for prevention or treatment of microinfarctions in humans. The purpose of the present study was to develop an experimental model useful for studying discrete microischemic foci. In order to achieve single cerebral microischemic foci plastic beads with diameters of about 100 microns were injected into the left heart ventricle of anesthetized rabbits. 2-Deoxy-[14C]glucose (2-DG) and autoradiography were used to detect regions with disturbed metabolism. The tissue sections were inspected for impacted beads. Foci with markedly increased 2-DG accumulation and with diameters of about 1 mm were detected in all parts of the brain, indicating hypoxic regions with enhanced glycolysis. In some foci, located mainly in the basal ganglia, a central dip in the 2-DG profile was seen, suggesting poor glucose supply to the central ischemic region. The ratio foci/beads was about 1 in the brain stem (diencephalon included) and about 0.5 in the cortex. Twenty-four hours after embolization, infarctions, mainly in the deeper brain regions, were seen. There were still foci with increased 2-DG uptake, which were mainly located in the cortex. The results suggest that microemboli reaching the deeper brain regions give rise to metabolic disturbances more often than emboli reaching the cortex and that the ischemic foci in deeper brain regions are more prone to develop further into infarctions.

Animals↗