Abstract Introduction The important factor during the application of substances for an inner ear therapy is the atraumatic execution as well as a homogeneous distribution over the cochlea in a reasonable time frame. Since faster delivery can be obtained with higher pressure but, higher pressure will lead to traumatic execution, there are certain constrains for the delivery process. Because of this, an optimized procedure for intracochlear delivery is needed, which enables reduction of intracochlear pressure during perfusion in reasonable time. Hence, the aim of this study was to compare different techniques of substance application and their effects on intracochlear pressure in different models. Material and Methods Intracochlear pressure was measured by fiberoptic pressure sensors in artificial cochlea models and in a human temporal bone. The pressure sensor was introduced into the inner ear models via an additional channel or the lateral arcade of the temporal bone. In all models the substance was applied by means of an inner ear catheter (MED-EL, Innsbruck, Austria) via the round window with methylene blue with or without second access to the cochlea (helicotrema/oval window). Results The application of substances showed significant differences in intracochlear pressure and substance distribution at the same velocity between the models with and without second access. Conclusion Using a second-hole technique leads to a faster homogeneous distribution, as well as a lower intracochlear pressure, which can be assumed to be an essential factor for hearing preservation during substance application.
Recombinant human interleukin 11 (rhIL-11) is a pleiotropic cytokine that stimulates bone marrow stem cells to proliferate and decreases intestinal mucosal injury produced by cytoablative drugs and radiation in animals. The effects of rhIL-11 were studied in a hamster model of oral mucositis and in two rat models of inflammatory bowel disease (IBD). Oral mucositis was induced in male Golden Syrian hamsters with 5-fluorouracil 60 mg/kg intraperitoneal, days 0 and 2. Peak mucositis occurred by day 10 in vehicle treated animals. rhIL-11, given twice daily subcutaneously, decreased the mucositis in a dose-dependent manner and increased animal survival at all doses tested. In two models of IBD, the acetic acid-induced acute colonic injury model in Sprague-Dawley rats and the transgenic Fischer 344 rats expressing human HLA-B27 and beta 2-microglobulin, rhIL-11 decreased the gross and microscopic damage in the colons of these animals. These data suggest that rhIL-11 exerts effects on the gastrointestinal mucosa which ameliorate responses to injurious stimuli.
The ultrastructure of the serosal mesothelium of the stomach, and small and large intestine has been investigated for the first time by scanning and transmission electron microscopy in the normal piglet. Its fine structure is similar to that reported previously for the calf and rat visceral mesothelium and is notable for the presence of abundant, long, widely spaced microvilli extending from the apical surface of mesothelial cells. Large rough endoplasmic reticula, free ribosomes, and pinocytotic vesicles were numerous, but Golgi apparatuses, mitochondria, lysosomes, and other intracellular inclusions were scarce. Little difference was observed between the serosal mesothelium of the three regions investigated. This information on the normal piglet mesothelium may be useful for future studies of pathogenesis of experimentally induced peritoneal adhesions, since the immature animal is at elevated risk and the porcine digestive tract resembles that of the human.
The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.
Pemphigus foliaceus is an uncommon dermatologic disorder occurring in several species and has been reported in horses during the past decade. An ultrastructural analysis of affected skin of horses presenting to our clinics has revealed early cytopathologic features of pemphigus-like disease, some of which closely resemble pemphigus foliaceus in the human, calve, and guinea pig. Prior to complete acantholysis and bullae formation, the intercellular spaces enlarged, but intercellular bridges and desmosomes remained intact. A novel finding was presence of aggregates of electron dense granular material which were seen in intercellular spaces of the epidermal basal cell layer, and may represent antigen-autoantibody complexed material or deranged cement substances. Other changes preceding acantholysis consisted of mild dyskeratosis, reduction of peripheral tonofilaments, enlargement of rough endoplasmic reticula, cytoplasmic vacuolization, and mitochondrial damage in epidermal cells. In more severe lesions where bullae were present and acantholysis was observed, bacterial invasion and leucocytic infiltration were evident in all epidermal layers, and corneal cells displayed cytoplasmic vacuolization and retention of nuclei. Basal cells remained intact, though intercellular spaces were enlarged on apical and lateral boundaries. The pathogenesis of this disease in the horse appeared morphologically similar to a pemphigus autoimmune disorder and its variants in other species, and morphologic evidence is provided to suggest that some cellular metabolic derangements may be concurrent with the extracellular events or cell peripheral changes that precede acantholysis and bullae formation.
In the present investigation 42 female ferrets were studied in regard to the influence of canine distemper in this species on gastric acid secretion. A total of fifteen naturally-infected and 27 non-infected ferrets were fasted and pylorus-ligated, and were either injected with corticosterone (10 or 50 mg/kg, s.c. one injection/day for 4 days) suspended in corn oil, injected with corn oil, on non-injected. Prior to autopsy blood samples were acquired for corticosterone analysis, and at autopsy the volume, pH, free and combined acidity of the gastric contents were evaluated. It was apparent that distemper induced hypochlorhydria in ferrets under the conditions of these experiments, an effect which was probably mediated through the central nervous system, but may also relate to a direct effect of distemper virus upon the gastric mucosa. Administration of corticosterone did not prevent hypochlorhydria in distemperous ferrets. Blood levels of corticosterone were elevated due to the stress effect of distemper infection, and also as a reflection of exogenous corticosterone administration. Prior immunization against canine distemper failed to immunize the ferrets in this study against the natural precipitation of this disease.
Ethanol is known to have profound actions on the gastrointestinal tract. The present study was undertaken to examine the effects of ethanol on some of the natural antioxidant defensive enzymes in the gastrointestinal tract; the activities of these enzymes in the liver and the brain were also measured for comparison with those in the gastrointestinal tract. Oral administration of absolute ethanol induced severe gastric mucosal lesions and also damage in the small intestine, however the total superoxide dismutase was unaffected in the tissues measured. The glucose-6-phosphate dehydrogenase activity was reduced only in the stomach while the total glutathione was elevated in the small intestinal mucosa. The catalase activities were activated in the stomach, small and large intestines, and brain, but not in the liver which contained the highest concentration of the enzyme. The present findings indicate that endogenous hydrogen peroxide may be an important damaging agent towards biomolecules in different organs and the removal of this by catalase represents an important defensive mechanism against ethanol toxicity.
