Gastrointestinal stromal tumor associated with hypertrophic osteopathy in a dog

Background: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm rarely described in the veterinary routine. The aim of this study was to report a case of GIST accompanied by a periosteal reaction, suggestive ofhypertrophic osteopathy, in a dog.Case: An 11-year-old male dog had a history of progressive weight loss, difficulty in locomotion, and dyspnea. During clinical care, increased bone volume was observed. Blood samples were collected for a complete blood count and biochemicalanalysis. The dog also underwent thoracic radiography and abdominal ultrasonography. The test results revealed anemia,leukocytosis, hypocalcemia, hypoalbuminemia, and hypocholesterolemia. The radiographic images of the limbs showeda generalized periosteal reaction, and thoracic radiography indicated changes compatible with mild chronic lung disease.Ultrasonographic findings indicated a neoformation in the intestinal loop of the right mesogastric region and increasedvolume in the left testicle, both of which were indicative of neoplasia. Therefore, the dog was referred for surgery, whereinthe intestinal mass and both testes were removed; the intestinal mass and left testicle were subjected to histopathologicaldiagnosis. The results of the biopsies confirmed that the testicular neoplasm was a seminoma, whereas the intestinal nodulewas compatible with GIST, and immunohistochemical analysis was necessary to confirm the diagnosis. On the basis ofpositive labeling for the antibodies vimentin, desmin, S100, and c-kit, the diagnosis of GIST was confirmed. Therefore,the animal underwent metronomic chemotherapy with 12 mg/m2 cyclophosphamide every 24 h for 3 months, and thereafter every 48 h for 6 months. Moreover, the dog was periodically monitored via imaging (radiography of the anteriorand posterior limbs, abdominal ultrasonography, and computed tomography)...(AU)

Gastrointestinal stromal tumor associated with hypertrophic osteopathy in a dog

Background: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm rarely described in the veterinary routine. The aim of this study was to report a case of GIST accompanied by a periosteal reaction, suggestive ofhypertrophic osteopathy, in a dog.Case: An 11-year-old male dog had a history of progressive weight loss, difficulty in locomotion, and dyspnea. During clinical care, increased bone volume was observed. Blood samples were collected for a complete blood count and biochemicalanalysis. The dog also underwent thoracic radiography and abdominal ultrasonography. The test results revealed anemia,leukocytosis, hypocalcemia, hypoalbuminemia, and hypocholesterolemia. The radiographic images of the limbs showeda generalized periosteal reaction, and thoracic radiography indicated changes compatible with mild chronic lung disease.Ultrasonographic findings indicated a neoformation in the intestinal loop of the right mesogastric region and increasedvolume in the left testicle, both of which were indicative of neoplasia. Therefore, the dog was referred for surgery, whereinthe intestinal mass and both testes were removed; the intestinal mass and left testicle were subjected to histopathologicaldiagnosis. The results of the biopsies confirmed that the testicular neoplasm was a seminoma, whereas the intestinal nodulewas compatible with GIST, and immunohistochemical analysis was necessary to confirm the diagnosis. On the basis ofpositive labeling for the antibodies vimentin, desmin, S100, and c-kit, the diagnosis of GIST was confirmed. Therefore,the animal underwent metronomic chemotherapy with 12 mg/m2 cyclophosphamide every 24 h for 3 months, and thereafter every 48 h for 6 months. Moreover, the dog was periodically monitored via imaging (radiography of the anteriorand posterior limbs, abdominal ultrasonography, and computed tomography)...

Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.

PURPOSE: To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization. METHODS: The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression. RESULTS: In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization. CONCLUSIONS: The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term.

Design of prolonged release tablets using new solid acrylic excipients for direct compression.

The design of new excipients that extend the release of drugs from tablets over prolonged periods is essential in reaching enhanced therapeutic performances. In this sense, the objective of this study was to develop new excipients, based on acrylic monomers (ethyl acrylate, methyl methacrylate, and butyl methacrylate) for use in direct compression (DC). The polymeric excipients were prepared by suspension and emulsion polymerization reactions and were characterized by FTIR to confirm the polymerization reaction. For the success of direct compression, excipients must present good flow and compactability properties. Therefore, excipients were submitted to analysis of morphology (SEM), particle size and size distribution by laser diffraction, and powder density (bulk density and tapped density). The Carr index, Hausner ratio, flow ratio, and cotangent of the angle α were determined. Thereafter, the polymeric excipients were used to prepare inert matrices by DC using propranolol hydrochloride (PHCl) as a model drug. The tablets were evaluated for average weight, breaking force, and friability tests. The release profiles were determined, and the dissolution kinetics was studied. The results indicated that matrices prepared from excipients obtained by suspension polymerization (NWCB and PECB) presented a release of PHCl for a period exceeding 12h, most likely due to the higher micromeritic properties. The results suggested that the increase in the percentage of polymers, as well as in the compression time, resulted in a higher hardness of the matrix with a reduced rate release of the PHCl. Finally, in vitro preliminary tests showed that the polymeric excipients produced were non-toxic for the gingival fibroblasts.

Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery.

Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release.

[Detection of myocardial ischemia in chronic Chagas disease patients with atypic precordial pain by exercise and Holter tests]. / Detecção de isquemia miocárdica em chagásicos crônicos com precordialgia atípica pelos testes de esforço e Holter.

PURPOSE: To determine the incidence and characteristics of myocardial ischemia, as detected by stress electrocardiography and Holter monitoring in Chagas' patients whose main complaint was precordial pain. METHODS: Thirty-one consecutive patients with Chagas' disease diagnosed on the basis of clinical and serological tests, and precordial pain severe enough to warrant cardiac catheterization were studied. Mean age was 54.4 +/- 9.6 years, and 51% were males. EKG changes indicative of myocardial ischemia were sought during maximal exercise and also during 24-hour Holter monitoring. The detection of myocardial ischemia by each one of these tests was compared by Fischer exact test, and also correlated to anatomical and functional results of coronary angiography at rest and after standardized hyperventilation for detecting coronary vasospasm. RESULTS: Baseline EKG changes mainly associated with ventricular conduction defects precluded the analysis of the ST segment in 11 patients. Among the other 20 patients, 7(35%) had angina during the exercise test, of whom only 2(10%) showed concomitant ischemic ST changes: one had 90% stenosis in the circumflex branch and the other 50% reduction of luminal diameter in a intramyocardial segment of the left anterior descending coronary artery, undergoing further 30% constriction after hyperventilation, with pain and ST-elevation that responded to nitrate administration. Thus, a positive correlation between a positive EKG exercise test with accompanying symptoms, and organic/functional coronary artery disease was found (p = 0.03). Holter tracings of good quality were obtained in 16 patients. Angina-like symptoms occurred in 25% of these patients, without concomitant ischemic or dysrhythmic EKG changes. Conversely, silent ischemia was detected in 1 (5%) patient during exercise and in 3 (18%) patients during the Holter monitoring. None of these patients had any evidence of organic or functional alterations in the coronary arteries. The absence of significant (> 50%) narrowing of the coronary arteries, at baseline and after hyperventilation, was also documented in the 11 patients in whom no valid EKG tracings were obtained for analysis. CONCLUSION: EKG-based methods for detecting myocardial ischemia are of limited value in the general population with Chagas' disease presenting with precordial pain, due to the high prevalence of baseline ST changes. The overall incidence of significant coronary artery disease, as detected by angiography, was low but not negligible in this population of Chagas' patients with precordial pain (4%). Nevertheless, a positive EKG test based on ST changes and accompanying pain has a 100% positive predictive accuracy for the presence of organic or functional coronary abnormalities. No additional yield was obtained with Holter monitoring, for the elucidation of the pathophysiology of the precordial pain in Chagas' patients with atypical angina. The significance of episodes of silent ischemia in some of these patients, with angiographically normal coronary arteries, remains to be determined.