Oncolytic reovirus synergizes with chemotherapeutic agents to promote cell death in canine mammary gland tumor

The oncolytic effects of reovirus in various cancers have been proven in many clinical trials in human medicine. Oncolytic virotherapy using reovirus for canine cancers is being developed in our laboratory. The objective of this study was to examine the synergistic anti-cancer effects of a combination of reovirus and low doses of various chemotherapeutic agents on mammary gland tumors (MGTs) in dogs. The first part of this study demonstrated the efficacy of reovirus in canine MGTs in vitro and in vivo. Reovirus alone exerted significant cell death by means of caspase-dependent apoptosis in canine MGT cell lines. A single injection of reovirus impeded growth of canine MGT tumors in xenografted mice, but was insufficient to induce complete tumor regression. The second part of this study highlighted the anti-tumor effects of reovirus in combination with low doses of paclitaxel, carboplatin, gemcitabine, or toceranib. Enhanced synergistic activity was observed in the MGT cell line treated concomitantly with reovirus and in all the chemotherapeutic agents except toceranib. In addition, combining reovirus with paclitaxel or gemcitabine at half dosage of half maximal inhibitory concentration (IC₅₀) enhanced cytotoxicity by activating caspase 3. Our data suggest that the combination of reovirus and low dose chemotherapeutic agents provides an attractive option in canine cancer therapy.     

Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines

Objective-To evaluate in vitro effects of gemcitabine alone and in combination with carboplatin on canine transitional cell carcinoma (TCC) cell lines. Sample-In vitro cultures of 5 canine TCC cell lines. Procedures-Cells were treated with gemcitabine, carboplatin, or a combination of both at various concentrations. Cell proliferation was assessed via a fluorescence-based microplate cell proliferation assay. Cell cycle was evaluated via propidium iodide staining, and apoptosis was assessed by measurement of caspase 3 and 7 enzymatic activity. Synergy between gemcitabine and carboplatin was quantified via combination index analyses. Results-Treatment of 5 canine TCC cell lines with gemcitabine or carboplatin decreased cell proliferation, increased apoptosis, and induced cell cycle arrest. Cell cycle arrest and apoptosis were markedly increased when cell lines were treated with both gemcitabine and carboplatin simultaneously or sequentially. Order of administration during sequential treatment did not consistently affect cell proliferation results in TCC cell lines. When TCC cell lines were treated with gemcitabine and carboplatin in combination at therapeutically relevant concentrations (gemcitabine concentration, < 10μM; carboplatin concentration, < 250μM), a significant decrease in cell proliferation was observed, compared with cell proliferation following treatment with gemcitabine or carboplatin alone. In combination, the effects of gemcitabine and carboplatin were synergistic in 3 of 5 cell lines and additive in the other 2. Conclusions and Clinical Relevance-Gemcitabine had antitumor effects on canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had synergistic activity at biologically achievable concentrations.     

Effect of partial ureteral obstruction on results of renal scintigraphy in dogs

OBJECTIVE: To use scintigraphy to determine the effects of partial ureteral obstruction on renal transit time and induction of diuresis in dogs. ANIMALS: 8 adult dogs. PROCEDURE: Scintigraphy was performed, using technetium Tc 99m diethylenetriaminepentacetic acid (Tc 99m-DTPA), before and within 2 weeks after surgical induction of unilateral partial ureteral obstruction. Time of peak (TOP) for the parenchyma (pTOP) and whole kidney (wTOP) and mean-transit time (MTT) for the parenchyma (pMTT) and whole kidney (wMTT) were determined by evaluation of renal time-activity curves before and after deconvolution analysis. Percentage uptake for each kidney between 1 and 3 minutes after injection of Tc 99m-DTPA was determined and used to indicate glomerular filtration rate. The effect of diuresis was determined by measuring the slope of decrease in activity after i.v. administration of furosemide. Obstruction was documented by direct inspection of the ureter. RESULTS: There was a concomitant increase in pTOP, wTOP, pMTT, and wMTT of the kidney with the partially obstructed ureter in all dogs at various times between 2 and 9 days after surgery. Concurrently, renal time-activity curves changed shape. Percentage renal uptake of the affected kidney was decreased in 2 dogs. Response to furosemide injection was inconsistent for kidneys before surgery and for kidneys with obstructed and nonobstructed ureters after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Scintigraphy may be a useful procedure for the evaluation of renal function in dogs with ureteral obstruction. Induction of diuresis appears to be of little value for differentiating renal function in dogs with obstructed and nonobstructed ureters.     

Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia

Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia, vomiting, diarrhea, lethargy, and depression and contributes to the development of primary renal failure and soft tissue mineralization. Treatment of hypercalcemia includes diagnosis and treatment of the underlying disease process and some combination of excracellular fluid volume expansion by administration of fluids intravenously and administration of glococorticosteroids, salmon calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may be safe and effective in the treatment of hypercalcemia. The purpose of our study was to characterize the efficacy and safety of pamidronate in the treatment of hypercalcemia attritutable to several different disease processes in the dog and cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05-2.0 mg/kg IV for a variety of disease processes, including neoplasia (n = 4), calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia with chronic renal failure (n = 1). In all the animals, IV pamidronate administration rapidly decreased serum calcium concentrations without evident toxicosis. Two animals received pamidronate several times without obvious toxicosis. On the basis of the findings in our retrospective study, pamidronate may be a safe and effective drug with which to lower both serum total and ionized calcium concentrations in patients with hypercalcemia arising from a wide variety of underlying disease processes.     

Evaluation of transurethral cystoscopy and excretory urography for diagnosis of ectopic ureters in female dogs: 25 cases (1992-2000)

OBJECTIVE: To evaluate transurethral cystoscopy and excretory urography for diagnosis of ectopic ureter in female dogs and identify concurrent urogenital abnormalities. DESIGN: Retrospective study. ANIMALS: 25 female dogs. PROCEDURE: Medical records of female dogs that underwent transurethral cystoscopy, excretory urography, and ventral cystotomy were reviewed for signalment, history, physical examination findings, results of bacteriologic culture of urine, and surgical findings. Videotapes of transurethral cystoscopy and radiographic studies were reviewed systematically without knowledge of surgical findings. RESULTS: Ectopic ureters were diagnosed in 24 of 25 (96%) of the dogs, bilaterally in 22 of 24 (91.6%) dogs. Cystoscopic evaluation yielded a correct diagnosis in all dogs when results of ventral cystotomy were used as the diagnostic standard. Cystoscopic evaluation identified a terminal ureteral opening for all ureters. Urethral fenestrations, troughs, striping, and tenting were identified. Abnormalities of the vestibule were identified in all examinations available for review (24/25). The paramesonephric septal remnant and its association with ectopic ureters were identified and characterized by cystoscopy. Radiographic findings were discordant with surgical findings and correctly identified 36 of 46 (78.2%) ectopic ureters and 2 of 4 normal ureters. Hydroureter and renal abnormalities were associated with distal urethral ectopic ureters on radiographic evaluations. CONCLUSIONS AND CLINICAL RELEVANCE: Transurethral cystoscopy was accurate and minimally invasive for identification and classification of ectopic ureters in dogs. Contrast radiography had limitations in diagnosis of ectopic ureters. Cystoscopic findings and associated vaginal and vestibular abnormalities support abnormal embryologic development in the pathogenesis of ectopic ureters.     

Testing Usability of Butylated Hydroxytoluene in Conservation of Goat Semen

The objective of this study was to investigate whether butylated hydroxytoluene (BHT) could be used as a suitable supporter or alternative of egg yolk during preservation of goat spermatozoa. Three in vitro experiments and a fertility test were conducted to evaluate the effect of BHT on viability of chilled‐stored semen as well as motility and kidding rate of frozen‐thawed spermatozoa. In the first two experiments, ejaculates (n = 30/experiment) were collected from 10 bucks, split, diluted with egg yolk‐based and egg yolk‐free extenders supplemented with or without 0.3, 0.6, 2, 5 and 8 mm BHT and stored at 5°C for 168 h. In the third experiment, 30 ejaculates were collected from the above‐mentioned bucks, split and diluted with egg yolk‐free extenders supplemented with or without 0.3, 0.6 and 0.9 mm BHT and egg yolk‐based extenders supplemented with or without 5 mm BHT. Diluted semen was cooled to 5°C over a period of 4 h, frozen and thawed in the form of 0.3‐ml pellets. In the fertility test, 75 ejaculates were collected from two proven fertile bucks, split, diluted with egg yolk‐free extenders containing 0.6 mm BHT and egg yolk‐based extenders supplemented with or without 5 mm BHT, frozen and thawed as described above. An insemination volume of 0.6 ml containing 120–140 × 10⁶ progressively motile spermatozoa was used for a single cervical insemination of cloprostenol‐synchronized does (n = 230). The results showed that addition of 5 mm BHT to egg yolk‐deficient (2.5%) extenders significantly improved viability of chilled‐stored semen together with motility (48.5%) and fertility (62.5%) of frozen‐thawed spermatozoa. Replacement of egg yolk in semen extenders by 0.6 mm BHT could sustain not only viability of chilled‐stored semen but also post‐thaw motility (47.5%) and fertility (53.75%) of frozen‐thawed spermatozoa. In conclusion, supplementation of semen diluents with BHT can ameliorate preservability of goat sperm.     

Hematuria and transitional cell papilloma of the renal pelvis treated via unilateral nephrectomy in an alpaca

CASE DESCRIPTION: An 11-year-old 72-kg (158-lb) sexually intact female alpaca was examined for diagnosis and treatment of hematuria of 4 months' duration. CLINICAL FINDINGS: Pigmenturia was detected by the owner when the alpaca was 8 months pregnant. Radiographic, ultrasonographic, vaginal speculum, and cystoscopic evaluation of the urinary tract revealed normal vaginal and urethral epithelia and increased bladder vessel tortuosity, with pulses of hemorrhage from the left ureter. Regenerative anemia and mild leukopenia were detected and serum urea nitrogen and creatinine concentrations were within reference ranges. TREATMENT AND OUTCOME: Chronic hematuria resolved after unilateral nephrectomy of the left kidney, and no dysfunction was detected in the remaining kidney. Histologic evaluation of the kidney revealed a transitional cell tumor in the renal pelvis. CLINICAL RELEVANCE: Although anemia is common in South American camelids, hematuria is an uncommon sign of this condition. Chronic urinary tract infection, toxin ingestion, and neoplasia causing hematuria or hemoglobinuria should be considered in South American camelids with pigmenturia. Thorough and systematic evaluation of the urinary tract should be performed to locate the site of hemorrhage to treat hematuria appropriately.     

The Current State of Solar Modeling

Data from the Global Oscillation Network Group (GONG) project and other helioseismic experiments provide a test for models of stellar interiors and for the thermodynamic and radiative properties, on which the models depend, of matter under the extreme conditions found in the sun. Current models are in agreement with the helioseismic inferences, which suggests, for example, that the disagreement between the predicted and observed fluxes of neutrinos from the sun is not caused by errors in the models. However, the GONG data reveal subtle errors in the models, such as an excess in sound speed just beneath the convection zone. These discrepancies indicate effects that have so far not been correctly accounted for; for example, it is plausible that the sound-speed differences reflect weak mixing in stellar interiors, of potential importance to the overall evolution of stars and ultimately to estimates of the age of the galaxy based on stellar evolution calculations.