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Case series summary: Malignant basal cell tumours may be seen on or near the nasal planum in cats, and include basal cell carcinomas, which are common, and basosquamous carcinomas, which are rare. Reported treatments for these tumours include surgical excision, radiotherapy, photodynamic therapy and cryosurgery. This report describes the successful management of basal cell tumours with electrochemotherapy (ECT), including calcium electroporation, in three cats. Relevance and novel information: All patients had a complete response lasting at least 9 months to 1 year. The adverse effects of this treatment were minimal and were limited to nasal discharge, sneezing and scabs at the treatment site. ECT and calcium electroporation are a safe, minimally invasive and effective option for the treatment of feline basal cell carcinoma and basosquamous carcinomas.
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PURPOSE: To quantify the surgical blood loss during canine enucleation and to investigate the relationship between this and any patient, surgical, and anesthetic factors. METHODS: A prospective observational analysis was conducted on 121 client-owned dogs (130 eyes) undergoing enucleation at a referral ophthalmology clinic. Blood loss was estimated by the gravimetric method (weight difference between dry and blood-containing surgical materials) to provide absolute blood loss (ABL) in milliliters, expressed as a percentage of circulating blood volume, to establish relative blood loss (RBL). RESULTS: Median ABL was 12 ml (1.6-116 ml), and median RBL was 1.3% (0.1%-6.7%). A higher RBL was associated with the following: use of a bupivacaine splash block versus retrobulbar nerve block (1.9 vs. 1%; p < .001), transpalpebral versus subconjunctival approach (2.2 vs. 1.3%; p = .003), and small versus large breed dogs (1.7% vs. 1.1%; p = .001). Both ABL and RBL differed significantly between surgeons. There was no significant difference in hemorrhage associated with the presence of ocular hypertension, systemic illness, surgical time, administration of meloxicam or choice of pre-medicant (acepromazine vs medetomidine). No dog required supportive intervention in response to surgical hemorrhage. CONCLUSIONS: This study has established a surgical blood loss estimate for dogs undergoing enucleation at an ophthalmology referral centre. Subconjunctival enucleation may be preferred for patients at greater risk of haemodynamic complications.
Subject(s)
Dog Diseases , Nerve Block , Dogs , Animals , Blood Loss, Surgical/veterinary , Bupivacaine , Acepromazine , Nerve Block/veterinary , Dog Diseases/surgeryABSTRACT
Iron is a key micronutrient for ocean phytoplankton, and the availability of iron controls primary production and community composition in large regions of the ocean. Pennate diatoms, a phytoplankton group that responds to iron additions in low-iron areas, can have highly variable iron contents, and some groups such as Pseudo-nitzschia, are known to use ferritin to store iron for later use. We quantified and mapped the intracellular accumulation of iron by a natural population of Pseudo-nitzschia from the Fe-limited equatorial Pacific Ocean. A total of 48 h after iron addition, nearly half of the accumulated iron was localized in storage bodies adjacent to chloroplasts believed to represent ferritin. Over the subsequent 48 h, stored iron was distributed to the rest of the cell through subsequent growth and division, partially supporting the iron contents of the daughter cells. This study provides the first quantitative view into the cellular trafficking of iron in a globally relevant phytoplankton group and demonstrates the unique capabilities of synchrotron-based element imaging approaches.
Subject(s)
Diatoms , Diatoms/metabolism , Ferritins , Iron/metabolism , Pacific Ocean , Phytoplankton/metabolismABSTRACT
OBJECTIVE: To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration. SERIES SUMMARY: Three cases were treated with meloxicam for variable nonspecific signs including lethargy and pyrexia. Hemorrhagic diarrhea developed following meloxicam administration in 2 cases. Gastrointestinal perforation was suspected on diagnostic imaging leading to exploratory celiotomy in all 3 cases. Partial colectomy was performed in 2 cases and suture repair with serosal patching in 1 followed by broad spectrum antimicrobials. All 3 dogs recovered from surgery well. One dog that had undergone perineal herniorrhaphy and received meloxicam perioperatively collapsed and died 7 days postsurgery. Postmortem examination revealed ulceration and perforation of the ascending colon with resultant generalized septic peritonitis. Histopathologic findings in all cases showed full thickness infiltration of the colonic wall with inflammatory cells along with ulceration and perforation. Thrombosis of vessels underlying the ulcerated areas was also noted. NEW OR UNIQUE INFORMATION PROVIDED: This report suggests that colonic perforation may be a complication of nonsteroidal anti-inflammatory drug use in some cases. To the authors' knowledge, this has not previously been described in dogs. Colonic perforation associated with NSAIDs administration may be more commonly identified in dogs with concurrent morbidities. Caution may be warranted when using NSAIDs in dogs with colonic pathology or possible risk factors to develop such pathology. Prompt diagnosis and treatment is essential for a positive outcome.
Subject(s)
Dog Diseases , Intestinal Perforation , Peritonitis , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Dog Diseases/diagnosis , Dogs , Intestinal Perforation/chemically induced , Intestinal Perforation/complications , Intestinal Perforation/veterinary , Meloxicam/adverse effects , Peritonitis/veterinaryABSTRACT
Carcinomatosis and sarcomatosis describe the widespread dissemination of metastatic neoplastic cells throughout the body. Studies describing their clinical and imaging features in veterinary patients are limited. The objective of this retrospective, multicenter, cross-sectional study is to describe the clinical, ultrasonographic, and CT features of pleural and peritoneal carcinomatosis and sarcomatosis in dogs and cats to aid detection and differentiation of these lesions. Medical records and CT and ultrasonographic images were reviewed. Although a large degree of overlap was observed between the imaging features and clinical signs of canine and feline carcinomatosis and sarcomatosis, some distinguishing features were observed. Dogs were significantly more likely to present with abdominal pain compared to cats (P = .022), whereas cats more commonly presented with inappetence (P = .019). Dogs with sarcomatosis had a significantly heavier bodyweight than dogs with carcinomatosis (P = .005), largely due to a higher prevalence of splenic hemangiosarcoma in this patient cohort. Peritoneal effusion was more frequently observed in dogs with carcinomatosis compared to dogs with sarcomatosis (P = .021). Imaging and clinical features observed in this study may help to distinguish sarcomatosis and carcinomatosis lesions. Due to the large degree of overlap observed, cytological or histopathological analysis is recommended for definitive diagnosis.
Subject(s)
Carcinoma/veterinary , Cat Diseases/diagnostic imaging , Dog Diseases/diagnostic imaging , Pleural Neoplasms/veterinary , Tomography, X-Ray Computed/veterinary , Ultrasonography/veterinary , Animals , Carcinoma/diagnostic imaging , Cat Diseases/pathology , Cats , Cross-Sectional Studies , Dog Diseases/pathology , Dogs , Male , Peritoneal Neoplasms/veterinary , Pleural Neoplasms/diagnostic imaging , Retrospective Studies , Soft Tissue Neoplasms/veterinary , Tomography, X-Ray Computed/methods , Ultrasonography/methodsABSTRACT
BACKGROUND: Lymphatic vascular malformations are rare findings in canine patients with six reports available in veterinary literature. Retroperitoneal cystic lymphatic malformations have not been described previously in canine patients and neither has the use of immunohistochemistry to determine their origin, i.e. vascular versus lymphatic. CASE PRESENTATION: An 8-year-old neutered female Cocker spaniel was referred for pollakiuria, dysuria and a painful abdomen. Computed tomography scanning of the abdomen showed a fluid filled structure adjacent to the urinary bladder. During surgical exploration, a thin walled cystic structure with sero-haemorrhagic fluid was found, extending from the retroperitoneal space into the abdomen. The mass was excised and submitted for histopathology, revealing a cystic mass lined by a fibrovascular capsule within the retroperitoneal/mesenteric adipose tissue. The inner surface of the cyst was lined by a single layer of bland, flattened spindle cells. Intramural blood vessels were well differentiated, with perivascular haemorrhage. On recurrence 11 months later, the mass was excised for the second time and a PleuralPort (Norfolk Animal products) was placed. Fifteen months after initial presentation, progression occurred with haemorrhagic fluid in the cystic space, pleural- and abdominal cavities and the owners opted for euthanasia. Histopathology and positive immunohistochemistry for lymphatic markers lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) and prospero homeobox protein-1 (PROX-1) confirmed a lymphatic vascular origin of the cystic structure. CONCLUSIONS: To our experience, a definitive diagnosis of retroperitoneal cystic malformation of lymphatic origin could be done only by combining the clinical presentation, advanced imaging, histopathology and LYVE-1 and PROX-1 immunohistochemistry. This is the first report of a vascular malformation in a dog where immunohistochemistry was used to make a final diagnosis. A lymphatic malformation, even if rare, should be added on the list of the differential diagnosis in a patient with a retroperitoneal cystic structure containing serohaemorrhagic fluid. Results of this case report can aid in diagnosis of future cases, however, further studies on therapy and management are needed to provide additional information about optimal treatment of these patients.
Subject(s)
Dog Diseases/pathology , Retroperitoneal Neoplasms/veterinary , Retroperitoneal Space/pathology , Animals , Dog Diseases/diagnostic imaging , Dog Diseases/surgery , Dogs , Euthanasia, Animal , Female , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/surgery , Retroperitoneal Space/diagnostic imaging , Retroperitoneal Space/surgery , Tomography, X-Ray Computed/veterinaryABSTRACT
The article aims to demonstrate the susceptibility to death that certain Amazonian peoples are facing, as a consequence of their particular migratory demography, which instead of being curbed, have been exponentially intensified by the outbreak of Sars-CoV-19. The article offers an account of the "pendular migrations" and "return migrations" that the indigenous and black rural populations of that region carry out as a result of daily labor displacements, in the search for medical-hospital assistance and the consolidation of political and legal visibility within the cities. In a second effort, directly related to the previous one, we articulate the interference of the viral threat not on the contingency of population flow, but on the dangerous intensification of people circulation between the territorial nuclei of the "first habitation" and the average Amazonian cities, where, as a rule, these peoples maintain "second residences" and to where they regularly transmigrate. To illustrate this phenomenon, three accounts of different Brazilian Amazonian realities are reported: on the rural black population of the banks of the Turiaçu River, Maranhão state, the indigenous people of the savannah Lavrado, of the northeast of Roraima state, and the Mura people, who live in the southeast region of Amazonas state. On these realities, the cosmographies of the mobility of their populations are challenged by the changes and strategic conditions imposed by the pandemic.
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CASE SUMMARY: A 14-year-old neutered female Burmese cat was referred for investigation of a caudal oropharyngeal mass. CT showed a thin walled cyst-like structure filling and expanding from the right tympanic bulla. Histopathology showed fragments of mildly dysplastic squamous epithelium and aggregates of keratin. These findings were considered consistent with a diagnosis of cholesteatoma. RELEVANCE AND NOVEL INFORMATION: To the best of our knowledge, this is the first reported case of a cholesteatoma in a cat. Cholesteatoma should be considered a differential diagnosis for cats presenting with a caudal oropharyngeal mass, a history of chronic ear disease or a history of previous, surgically managed middle ear disease. Advanced imaging and biopsies should be considered important in the diagnosis of these lesions.
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OBJECTIVE: To compare precorrectional and postcorrectional femoral alignment following distal femoral osteotomy using patient-specific 3-dimensional (3D)-printed osteotomy and reduction guides in vivo and ex vivo. STUDY DESIGN: Prospective study. SAMPLE POPULATION: Ten client-owned dogs and matching 3D-printed plastic bone models. METHODS: Distal femoral osteotomy was performed via a standard approach using osteotomy and reduction guides developed with computer-aided design software prior to 3D-printing. Femoral osteotomy and reduction was also performed on 3D-printed models of each femur with identical reprinted guides. Femoral varus angle (FVA) and femoral torsion angle (FTA) were measured on postoperative computed tomographic images by 3 observers. RESULTS: In vivo, the mean difference between target and achieved postoperative was 2.29° (±2.29°, P = .0076) for the FVA, and 1.67° (±2.08°, P = .300) for the FTA. Ex vivo, the mean difference between target and achieved postoperative was 0.29° (±1.50°, P = .813) for the FVA, and -2.33° (±3.21°, P = .336) for the FTA. Intraobserver intraclass correlation coefficients (ICC; 0.736-0.998) and interobserver ICC (0.829 to 0.996) were consistent with an excellent agreement. CONCLUSION: Use of 3D-printed osteotomy and reduction guides allowed accurate correction of FTA in vivo and both FVA and FTA ex vivo. CLINICAL SIGNIFICANCE: Use of 3D-printed osteotomy and reduction guides may improve the accuracy of correction of femoral alignment but warrant further evaluation of surgical time, perioperative complications, and patient outcomes compared with conventional techniques.
Subject(s)
Dogs/injuries , Models, Anatomic , Osteotomy/veterinary , Patellar Dislocation/veterinary , Printing, Three-Dimensional , Animals , Femur/surgery , Humans , Osteotomy/methods , Patella/surgery , Patellar Dislocation/surgery , Prospective Studies , Plastic Surgery Procedures/veterinary , Tomography, X-Ray ComputedABSTRACT
CASE SUMMARY: A solitary, sessile, non-ulcerated, freely mobile cutaneous mass approximately 1 cm in diameter on the left temporal region of a 7-year-old neutered female cat was examined. A fine-needle aspirate and wedge biopsy were performed by the referring veterinary surgeon and indicated a neoplasm of uncertain cell lineage. On histopathological examination, the deep dermis contained a discrete, non-encapsulated and vascular neoplasm with morphological and immunophenotypical features typical of a glomus cell tumour. Neoplastic cells were immunopositive for vimentin, muscle actin and smooth muscle actin, and immunonegative for cytokeratin, S100, desmin and von Willebrand factor (factor VIII-related antigen). RELEVANCE AND NOVEL INFORMATION: Glomus cell tumours arise from modified smooth muscle cells and are rare in animals, particularly cats. Specific immunohistochemistry is of fundamental importance in the correct diagnosis of these tumours and should be considered for masses when cytology and histology results are inconclusive or uncertain.
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Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an intramuscular location. Medical records at 2 referral centers in the UK were examined to find cases of MCTs in this location. Seven dogs were identified as having an intramuscular MCT by a combination of fine-needle aspirate cytology and computed tomography or ultrasound. None of the dogs had evidence of local lymph node metastasis. Six dogs had no evidence of distant metastasis and surgery was carried out as the primary treatment option. Three of those dogs also had adjunctive chemotherapy due to a high Ki67 value or high mitotic index. All 6 dogs that had had surgery were alive at follow-up with a minimum elapsed time of 7 months. One dog had a course of chemotherapy due to the location, size, and evidence of biological activity of the tumor and died 23 days afterwards. The prognosis of intramuscular mast cell tumors appears to be favorable in most cases.
Tumeurs à mastocytes intramusculaires chez sept chiens. Les tumeurs à mastocytes (MCT) sont couramment observées chez les chiens et elles sont signalées à des emplacements cutanés, conjonctivaux, gastrointestinaux et dans les muqueuses orales, mais non dans des régions intramusculaires. Les dossiers médicaux de deux centres spécialisés du Royaume-Uni ont été examinés afin de trouver des cas de MCT à cet endroit. Sept chiens ont été identifiés comme ayant un MCT intramusculaire en utilisant une combinaison de cytologie par aspiration à l'aiguille fine et de tomodensitométrie ou d'échographie. Aucun des chiens ne présentait des signes de métastase des ganglions lymphatiques locaux. Six chiens ne manifestaient aucun signe de métastase distante et la chirurgie a été réalisée comme option de traitement primaire. Trois de ces chiens ont aussi subi une chimiothérapie d'appoint en raison d'une valeur élevée de Ki67 ou d'un indice mitotique élevé. Les six chiens qui avaient subi la chirurgie étaient vivants au suivi avec un délai écoulé de 7 mois. Un chien a subi un traitement de chimiothérapie en raison de l'emplacement, de la taille et de signes d'activité biologique de la tumeur et est mort 23 jours plus tard. Le pronostic de tumeurs à mastocytes intramusculaires semble être favorable dans la plupart des cas.(Traduit par Isabelle Vallières).
Subject(s)
Dog Diseases/diagnosis , Mast-Cell Sarcoma/veterinary , Animals , Dogs , Mast-Cell Sarcoma/diagnosis , Neoplasm Staging/veterinary , PrognosisABSTRACT
Six clones of the marine cyanobacterium Synechococcus, representing four major clades, were all found to contain significant amounts of silicon in culture. Growth rate was unaffected by silicic acid, Si(OH)4 , concentration between 1 and 120 µM suggesting that Synechococcus lacks an obligate need for silicon (Si). Strains contained two major pools of Si: an aqueous soluble and an aqueous insoluble pool. Soluble pool sizes correspond to estimated intracellular dissolved Si concentrations of 2-24 mM, which would be thermodynamically unstable implying the binding of intracellular soluble Si to organic ligands. The Si content of all clones was inversely related to growth rate and increased with higher [Si(OH)4 ] in the growth medium. Accumulation rates showed a unique bilinear response to increasing [Si(OH)4 ] from 1 to 500 µM with the rate of Si acquisition increasing abruptly between 80 and 100 µM Si(OH)4 . Although these linear responses imply some form of diffusion-mediated transport, Si uptake rates at low Si (~1 µM Si) were inhibited by orthophosphate, suggesting a role of phosphate transporters in Si acquisition. Theoretical calculations imply that observed Si acquisition rates are too rapid to be supported by lipid-solubility diffusion of Si through the plasmalemma; however, facilitated diffusion involving membrane protein channels may suffice. The data are used to construct a working model of the mechanisms governing the Si content and rate of Si acquisition in Synechococcus.
Subject(s)
Silicic Acid/metabolism , Silicon/metabolism , Synechococcus/metabolism , Synechococcus/growth & developmentABSTRACT
OBJECTIVE: To (i) correlate B-mode ocular ultrasound (US) and computed tomography (CT) (prospective pilot study), (ii) establish a reliable method to measure the normal canine eye using CT, (iii) establish a reference guide for some dog breeds, (iv) compare eye size between different breeds and breed groups, and (v) investigate the correlation between eye dimensions and body weight, gender, and skull type (retrospective study). PROCEDURE: B-mode US and CT were performed on ten sheep cadaveric eyes. CT biometry involved 100 adult pure-bred dogs with nonocular and nonorbital disease, representing eleven breeds. Eye length, width, and height were each measured in two of three planes (horizontal, sagittal, and equatorial). RESULTS: B-mode US and CT measurements of sheep cadaveric eyes correlated well (0.70-0.71). The shape of the canine eye was found to be akin to an oblate spheroid (a flattened sphere). A reference guide was established for eleven breeds. Eyes of large breed dogs were significantly larger than those of medium and small breed dogs (P < 0.01), and eyes of medium breed dogs were significantly larger than those of small breed dogs (P < 0.01). Eye size correlated with body weight (0.74-0.82) but not gender or skull type. CONCLUSIONS: Computed tomography is a suitable method for biometry of the canine eye, and a reference guide was established for eleven breeds. Eye size correlated with breed size and body weight. Because correlation between B-mode US and CT was shown, the obtained values can be applied in the clinical setting, for example, for the diagnosis of microphthalmos and buphthalmos.
Subject(s)
Eye/diagnostic imaging , Animals , Biometry , Body Weight , Dogs , Eye/anatomy & histology , Organ Size , Pilot Projects , Prospective Studies , Reference Standards , Retrospective Studies , Sheep , Species Specificity , Tomography, X-Ray Computed/veterinary , Ultrasonography/veterinaryABSTRACT
Human activity is accelerating changes in biotic communities worldwide. Predicting impacts of these changes on ecosystem services such as denitrification, a process that mitigates the consequences of nitrogen pollution, remains one of the most important challenges facing ecologists. Wetlands especially are valued as important sites of denitrification, and wetland plants are expected to have differing effects on denitrification. We present the results of a meta-analysis, conducted on 419 published estimates of denitrification in wetlands dominated by different plant species. Plants increased denitrification rates by 55% on average. This effect varied significantly among communities as defined by the dominant plant species, but surprisingly did not differ substantially among methods for measuring denitrification or among types of wetlands. We conclude that mechanistically linking functional plant traits to denitrification will be key to predicting the role of wetlands in nitrogen mitigation in a changing world.
Subject(s)
Denitrification , Plant Physiological Phenomena , Plants/classification , Wetlands , Environmental MonitoringABSTRACT
Mesozooplankton production in high-nutrient low-chlorophyll regions of the ocean may be reduced if the trace element concentrations in their food are insufficient to meet growth and metabolic demands. We used elemental microanalysis (SXRF) of single-celled plankton to determine their trace metal contents during a series of semi-Lagrangian drift studies in an HNLC upwelling region, the Costa Rica Dome (CRD). Cells from the surface mixed layer had lower Fe:S but higher Zn:S and Ni:S than those from the subsurface chlorophyll maximum at 22-30 m. Diatom Fe:S values were typically 3-fold higher than those in flagellated cells. The ratios of Zn:C in flagellates and diatoms were generally similar to each other, and to co-occurring mesozooplankton. Estimated Fe:C ratios in flagellates were lower than those in co-occurring mesozooplankton, sometimes by more than 3-fold. In contrast, Fe:C in diatoms was typically similar to that in zooplankton. RNA:DNA ratios in the CRD were low compared with other regions, and were related to total autotrophic biomass and weakly to the discrepancy between Zn:C in flagellated cells and mesozooplankton tissues. Mesozooplankton may have been affected by the trace element content of their food, even though trace metal limitation of phytoplankton was modest at best.
ABSTRACT
Mineral limitation of mesozooplankton production is possible in waters with low trace metal availability. As a step toward estimating mesozooplankton Fe and Zn requirements under such conditions, we measured tissue concentrations of major and trace nutrient elements within size-fractioned zooplankton samples collected in and around the Costa Rica Upwelling Dome, a region where phytoplankton growth may be co-limited by Zn and Fe. The geometric mean C, N, P contents were 27, 5.6 and 0.21 mmol gdw-1, respectively. The values for Fe and Zn were 1230 and 498 nmol gdw-1, respectively, which are low compared with previous measurements. Migrant zooplankton caused C and P contents of the 2-5 mm fraction to increase at night relative to the day while the Fe and Zn contents decreased. Fe content increased with size while Zn content decreased with size. Fe content was strongly correlated to concentrations of two lithogenic tracers, Al and Ti. We estimate minimum Fe:C ratios in large migrant and resident mixed layer zooplankton to be 15 and 60 µmol mol-1, respectively. The ratio of Zn:C ranged from 11 µmol mol-1 for the 0.2-0.5 mm size fraction to 33 µmol mol-1 for the 2-5 mm size fraction.
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Establishing relationships between biodiversity and ecosystem function is an ongoing endeavor in contemporary ecosystem and community ecology, with important practical implications for conservation and the maintenance of ecosystem services. Removal of invasive plant species to conserve native diversity is a common management objective in many ecosystems, including wetlands. However, substantial changes in plant community composition have the potential to alter sediment characteristics and ecosystem services, including permanent removal of nitrogen from these systems via microbial denitrification. A balanced assessment of costs associated with keeping and removing invasive plants is needed to manage simultaneously for biodiversity and pollution targets. We monitored small-scale removals of Phragmites australis over four years to determine their effects on potential denitrification rates relative to three untreated Phragmites sites and adjacent sites dominated by native Typha angustifolia. Sediment ammonium increased following the removal of vegetation from treated sites, likely as a result of decreases in both plant uptake and nitrification. Denitrification potentials were lower in removal sites relative to untreated Phragmites sites, a pattern that persisted at least two years following removal as native plant species began to re-colonize treated sites. These results suggest the potential for a trade-off between invasive-plant management and nitrogen-removal services. A balanced assessment of costs associated with keeping versus removing invasive plants is needed to adequately manage simultaneously for biodiversity and pollution targets.
Subject(s)
Fresh Water , Introduced Species , Nitrogen/metabolism , Poaceae/metabolism , Wetlands , Conservation of Natural Resources , Denitrification , Nitrification , Nitrogen/isolation & purification , Poaceae/growth & development , Typhaceae/growth & development , Typhaceae/metabolismABSTRACT
BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted.
Subject(s)
Antineoplastic Agents/pharmacology , Benzodiazepinones/pharmacology , Dog Diseases/drug therapy , Pyrroles/pharmacology , Animals , Cell Line, Tumor , Cross-Linking Reagents/pharmacology , DNA , Dogs , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Screening Assays, Antitumor , Female , Flow Cytometry , Mice , Mice, Nude , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To evaluate the effect of cuff presence and cuff inflation on airway pressure in an inspiratory model of canine tracheostomy. DESIGN: Ex vivo experimental study. Cadaver tracheas from Beagle dogs were attached aborally to a vacuum. Airway pressure and flow rate was measured before and after placement of tracheostomy tubes. ANIMALS: None. INTERVENTIONS: Adult uncuffed tubes and cuffed tracheostomy tubes (sizes 4, 6, 8, and 10) were placed within tracheas. Cuffs were investigated without inflation and at maximum cuff inflation. Airway pressure was measured at constant airflow rates at 30 and 60 L/min. MEASUREMENTS AND MAIN RESULTS: At set flow rates, airway pressures of tracheostomy tubes were compared to the intact trachea. A size 4 uncuffed tracheostomy tube showed the lowest airway pressure and a size 4 cuffed trachestomy tube with inflation showed the highest airway pressures. For sizes 6, 8, and 10 tubes, the presence of a cuff with and without inflation significantly increased airway pressure. Inflation of a cuff always significantly increased airway pressure. Similar pressure is seen between sizes 4 and 6 uncuffed tubes. CONCLUSIONS: Cuffed tracheostomy tubes should not be used unless specifically indicated due to increased airway pressure.