Biomedical subjects

D B DeNicola

Publications and source records attributed to D B DeNicola.

At least 19 recordsLinked to original sources

PubMed2005

Pretreatment tumor prostaglandin E2 concentration and cyclooxygenase-2 expression are not associated with the response of canine naturally occurring invasive urinary bladder cancer to cyclooxygenase inhibitor therapy.

The purpose of this study was to determine the extent to which pretreatment prostaglandin E2 (PGE2) concentration and cyclooxygenase-2 (cox-2) expression could be used to predict the antitumor activity of cox inhibitor treatment in naturally occurring canine transitional cell carcinoma of the urinary bladder (TCC). Snap frozen tissues (to measure PGE2) and formalin-fixed TCC samples (for cox-2 immunohistochemistry) were obtained by cystoscopy or surgery. Complete tumor staging was performed before and after one month of treatment with the cox inhibitor, piroxicam (0.3 mg/kg q24 h po). The pretreatment PGE2 concentration ranged from 57 to 1624 ng/g of TCC tissue; n=18 dogs). Cox-2 immunoreactivity was observed in all TCC samples. There was no association between PGE2 concentration, cox-2 expression, and change in tumor volume with piroxicam treatment. In conclusion, cox-2 expression or PGE2 concentration alone, or the combination of the two was not useful in predicting response to piroxicam treatment in canine TCC.

Animals↗

PubMed2004

Expression of cyclooxygenase-1 and 2 in naturally-occurring canine cancer.

The purpose of this work was to determine cox-1 and cox-2 expression by immunohistochemistry in forms of naturally occurring canine cancer in order to identify animal systems for pre-clinical evaluation of cox inhibitors and cox-2 inhibitors in cancer. Canine lymphoma (LSA), prostatic carcinoma (PCA), osteosarcoma (OSA), oral melanoma (MEL), oral squamous cell carcinoma (SCC), oral fibrosarcoma (FSA), mammary carcinoma (MCA), and normal tissues were included. Cox-2 was expressed in epithelial tumors (17 of 26 SCC, 8 of 13 MCA, 5 of 9 PCA cases) and MEL (9 of 15 cases), but was generally absent in normal tissues. Cox-2 expression was minimal or absent in mesenchymal tumors and LSA. Cox-1 was expressed in normal epithelial tissues and in some osteoclast and osteoblast in bone, but was absent in normal lymph node. In conclusion, forms of canine cancer were identified for in vivo studies of the effects of cox inhibitors and selective cox-2 inhibitors on cancer.

Animals↗

PubMed2001

Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs.

OBJECTIVE: To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs. DESIGN: Prospective case series. ANIMALS: 17 dogs with measurable oral squamous cell carcinoma. PROCEDURE: Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died. RESULTS: One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.

Animals↗

PubMed2001

Prostaglandin E2 concentrations in naturally occurring canine cancer.

The purpose of this study was to determine the PGE2 concentration in naturally-occurring cancer in pet dogs and in canine cancer cell lines in order to identify specific types of canine cancer with high PGE2 production which could serve as preclinical models to evaluate anticancer strategies targeting PGE2. PGE2 concentrations were measured by enzyme immunoassay in canine melanoma, soft tissue sarcoma, transitional cell carcinoma, osteosarcoma, and prostatic carcinoma cell lines; in 80 canine tumor tissue samples including oral melanoma (MEL), oral squamous cell carcinoma (SCC), transitional cell carcinoma of the urinary bladder (TCC), lymphoma (LSA), mammary carcinoma (MCA), osteosarcoma (OSA), prostatic carcinoma (PCA); and in corresponding normal organ tissues. High concentrations of PGE(2)(range 400-3300 pg/10(4)cells) were present in cell culture medium from the transitional cell carcinoma, prostatic carcinoma, and osteosarcoma cell lines. PGE2 concentrations in tumor tissues were elevated (tumor PGE2 concentration>mean+2X sd PGE(2)concentration of normal organ tissue) in 21/22 TCC, 5/6 PCA, 7/10 SCC, 5/10 MEL, 3/8 MCA, 4/15 OSA, and 0/9 LSA. Results of this study will help guide future investigations of anticancer therapies that target cyclooxygenase and PGE2.

Animals↗

PubMed2001

Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of pulmonary function in horses with inflammatory respiratory disease.

OBJECTIVE: To evaluate the association among clinical signs, results of cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and measures of pulmonary function in horses with inflammatory respiratory disease. ANIMALS: 9 healthy horses, 5 horses with inflammatory airway disease (IAD), and 9 horses with chronic obstructive pulmonary disease (COPD). PROCEDURES: Clinical examination, lung function tests, and BAL were performed on each horse. RESULTS: Standard lung mechanics of horses with exacerbated COPD differed significantly from those of healthy horses; however, there were few differences among horses with IAD, horses with COPD during remission, and healthy horses. Most variables for forced expiration (FE) in horses with COPD or IAD differed significantly from those for healthy horses. Results of clinical examination had low to moderate sensitivity and predictive values for a diagnosis of COPD (range, 67 to 80%). Results of FE tests had high sensitivity, specificity, and predictive values for a diagnosis of COPD (79 to 100%), and results of standard lung mechanics tests had low sensitivity and predictive values (22 to 69%). Percentage of neutrophils in BAL fluid was highly sensitive (100%) but moderately specific (64%) for a diagnosis of COPD. CONCLUSIONS AND CLINICAL RELEVANCE: Clinical examination is moderately accurate for establishing a diagnosis of COPD. Forced expiration tests can specifically detect early signs of airway obstruction in horses with COPD and IAD that may otherwise be inapparent. Cytologic evaluation of BAL fluid allows early detection of inflammatory respiratory disease, but it is not specific for COPD.

Animals↗

PubMed2000

Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer.

PURPOSE: More than 12,000 people are expected to die from invasive transitional cell carcinoma (TCC) of the urinary bladder each year in the United States, indicating that more effective therapy is needed. Drugs inhibiting cyclooxygenase (cox) have recently been found to have chemopreventive and antitumor activity and may potentiate the effects of chemotherapy. The purpose of this study was to determine whether cisplatin combined with the cox-inhibitor piroxicam would induce remission more frequently than cisplatin alone in a relevant animal model of human invasive TCC. METHODS: Pet dogs with naturally occurring, histopathologically confirmed, measurable TCC of the urinary bladder were randomized to receive cisplatin (60 mg/m2 i.v. every 21 days) or cisplatin (same dosage) combined with piroxicam (0.3 mg/kg orally every 24 h). Complete staging was performed prior to and at 6-week intervals during therapy. RESULTS: After eight dogs had been evaluated in each treatment group, a significant difference in remission rate was noted (Fisher's Exact test, P < 0.004). Tumor responses in the cisplatin/piroxicam group included two complete remissions (CR), four partial remissions (PR), two stable disease (SD), and no progressive disease (PD). Tumor responses to cisplatin alone in eight dogs were no CR, no PR, four SD, and four PD. Six additional dogs were treated with cisplatin/piroxicam, and in total 10 of 14 dogs had remission (two CR, eight PR). Renal toxicity of cisplatin/ piroxicam was frequent and dose limiting. CONCLUSIONS: Cisplatin/piroxicam induced remission more frequently than cisplatin alone in a canine model of human invasive TCC. Strategies to reduce renal toxicity need to be developed prior to evaluation of cisplatin/piroxicam in humans or general use of this treatment in pet dogs.

Animals↗

PubMed2000

Diagnosis of sporotrichosis in a donkey using direct fluorescein-labeled antibody testing.

A 4-year-old female donkey residing in an open field in Indiana was admitted for evaluation of facial lesions of 2 years duration. Cytologic and histologic examination of exudate and tissue from the lesions revealed a pyogranulomatous inflammatory reaction with numerous yeasts. Sporothrix schenckii was suspected to be the infectious agent; however, multiple culture attempts did not provide positive identification of the organism. Serologic examination supported infection with S. schenckii. A specific direct immunofluorescent antibody test performed on paraffin-embedded tissue sections confirmed the organism as S. schenckii. Clinical signs resolved after appropriate iodide therapy.

Animals↗

PubMed1999

Metabolism of styrene by mouse and rat isolated lung cells.

Styrene is pneumotoxic in mice. It is metabolized by pulmonary microsomes of both mouse and rat to styrene oxide (SO), presumed to be the toxic metabolite of styrene, and known to be genotoxic. To determine which pulmonary cell types are responsible for styrene metabolism, and which cytochromes P450 are associated with the bioactivation of styrene, we isolated enriched fractions of mouse and rat Clara and type II cells in order to determine the rate of styrene metabolism, with and without chemical inhibitors. Mouse Clara cells readily metabolized styrene to SO. Diethyldithiocarbamate, a CYP2E1 inhibitor, caused less inhibition of SO formation in Clara cells isolated from mice than previously found with pulmonary microsomes. As in microsomes, 5-phenyl-1-pentyne, a CYP2F2 inhibitor, inhibited the formation of both enantiomers. alpha-Naphthoflavone, a CYP1A inhibitor, did not inhibit SO formation in Clara cells. alpha-Methylbenzylaminobenzotriazole, a CYP2B inhibitor, exhibited minimal inhibition of SO production at 10 microM and less at 1 microM. The microsomal and isolated cell studies indicate that CYP2E1 and CYP2F2 are the primary cytochromes P450 involved in pulmonary styrene metabolism. Styrene metabolizing activity was much greater in Clara cells than in type II pneumocytes, which demonstrated essentially no activity. Styrene-metabolizing activity was several-fold higher in the mouse than in rat Clara cells. The more pneumotoxic and genotoxic form, R-SO, was preferentially formed in mice, and S-SO was preferentially formed in rats. These findings indicate the importance of Clara cells in styrene metabolism and suggest that differences in metabolism may be responsible for the greater susceptibility of the mouse to styrene-induced toxicity.

Animals↗

PubMed1999

Discospondylitis in association with an intra-abdominal abscess in a dog.

An 11-year-old German shepherd dog cross was presented with a six-week history of weight loss and abdominal distension. A diagnosis of abdominal abscess and discospondylitis was made. The dog responded to surgical excision of the abscess and conservative medical treatment for discospondylitis.

Abdominal Abscess↗

PubMed1999

Avian pox in sanderlings from Florida.

Asian pox was diagnosed in three sanderlings (Calidris alba) on Sanibel Island, Florida (USA) in February 1997. All three cases had large tumor-like lesions which contributed significantly to their mortality. Poxvirus infection was confirmed by cytology, histopathology, and electron microscopy. This is the first report of poxvirus infection in sanderlings.

Animals↗

PubMed1998

Minimal effects of acrylonitrile on pulmonary and hepatic cell injury enzymes in rats with induced cytochrome P450.

Acrylonitrile (AN) has many industrial applications but is a known carcinogen in animals and a suspect human carcinogen. Its toxicity is generally associated with its bioactivation, the initial step of which is epoxidation by cytochrome P450. While the hepatotoxicity and pneumotoxicity of AN in naive rats is generally low, the purpose of this study was to investigate the pneumotoxicity and hepatotoxicity of AN in adult male Sprague-Dawley rats and evaluate interactions with agents that may alter its metabolism. Five agents, phenobarbital, beta-naphthoflavone, pyridine, ethanol, and acetone, were administered prior to AN as inducers of CYP2B, CYP1A, and CYP2E1. Pneumotoxicity was measured as increases in y-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF). Hepatotoxicity was measured as increases in serum sorbitol dehydrogenase (SDH). AN (1 mmol/kg ip) had little effect on liver or lung, even when given following most of the inducing agents. AN (1.5 mmol/kg) caused an increase in GGT, but had little effect on SDH or LDH. Acetone plus AN caused an increase in mortality and some indication of pneumotoxicity, but lung and liver were histologically normal. Thus AN alone even at a high dose had no effect on the liver or lung and minimal effects following induction of cytochrome P450 by acetone.

Acetone↗

PubMed1996

Cisplatin treatment of transitional cell carcinoma of the urinary bladder in dogs: 18 cases (1983-1993).

OBJECTIVE: To determine whether cisplatin administered at a dosage of 60 mg/m2 of body surface area, IV, every 21 days, would induce remission of transitional cell carcinoma of the urinary bladder in dogs. DESIGN: Retrospective analysis of medical records. ANIMALS: 18 dogs with histologically confirmed transitional cell carcinoma of the urinary bladder. PROCEDURE: Clinical staging was performed by means of physical examination, contrast cystography or ultrasonography, and thoracic radiography prior to and 42 days after the initiation of cisplatin treatment. Dogs with clinical signs of tumor progression were reevaluated earlier than 42 days in some instances. Complete remission (CR) was defined as complete resolution of measurable tumor. Partial remission (PR) was defined as a > or = 50% reduction in tumor volume without development of new tumors. Stable disease was defined as < 50% change in tumor volume at 42 days without development of new lesions. Progressive disease (PD) was defined as > or = 50% increase in tumor volume or development of new tumors at any time. Dogs were reevaluated at 42-day intervals until they had a CR, developed PD, or developed unacceptable adverse effects. RESULTS: Three dogs had a PR, 4 had stable disease, and 9 had PD. Tumor response could not be assessed in 2 dogs: 1 dog developed grand mal seizures 3 hours after the first dose of cisplatin was given and was euthanatized; the other dog continued to have clinical signs of urinary tract obstruction and was euthanatized 8 days after the first dose of cisplatin. Four dogs developed renal azotemia that was suspected to be secondary to cisplatin nephrotoxicity. CLINICAL IMPLICATIONS: The cisplatin dosage was higher than that reported in studies of dogs with transitional cell carcinoma of the bladder. Even with this higher dosage, none of the dogs had a CR, and only 3 of 18 had a PR. A more effective, less toxic treatment for transitional cell carcinoma in dogs is needed.

Animals↗

PubMed1996

Pneumotoxicity and hepatotoxicity of styrene and styrene oxide.

The purpose of this study was to investigate the toxicity of styrene and styrene oxide in the lung in comparison to the toxicity in the liver. Pneumotoxicity caused by styrene or styrene oxide was measured by elevations in the release of gamma-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) into bronchoalveolar lavage fluid (BALF), while hepatotoxicity was measured by increases in serum sorbitol dehydrogenase (SDH) in non-Swiss Albino (Hsd:NSA) mice. Intraperitoneal administration of styrene at doses of 500-1000 mg/kg caused consistent dose-dependent increases in both sets of biomarkers with the hepatic effect appearing earlier than the pulmonary effect. Pyridine, phenobarbital, and beta-naphthoflavone, inducers of CYP2E1, CYP2B, and CYP1A, respectively, increased the toxicity of styrene. Pyridine and phenobarbital treatments increased mortality due to styrene. Styrene oxide exists in two enantiomeric forms: (R)- and (S)-styrene oxide, and the differential toxicities of the two enantiomers and racemic styrene oxide were compared. In all studies, (R)-styrene oxide caused greater toxicity than the (S) enantiomer, especially in the liver. Trichloropropene oxide, an epoxide hydrolase inhibitor, was used to inhibit styrene oxide detoxification and increased its hepatotoxicity, while buthionine sulfoxamine, a glutathione depletor, did not. These results demonstrated the greater role of epoxide hydrolase in styrene oxide detoxification.

Animals↗

PubMed1996

Nephrotoxicity of amphotericin B administered to dogs in a fat emulsion versus five percent dextrose solution.

OBJECTIVE: To determine whether administration of amphotericin B in a fat emulsion solution would reduce the nephrotoxicity of amphotericin B, compared with that associated with administration of amphotericin B in 5% dextrose solution. DESIGN: Prospective controlled study. ANIMALS: 2 groups of 5 adult male Beagles. PROCEDURE: Dogs received amphotericin B (1 mg/kg of body weight/d) prepared in 5% dextrose solution or in 20% fat emulsion daily for 6 doses. Serum biochemical analysis, CBC, urinalysis, and endogenous creatinine clearance was performed on days 0 and 8, 2 days after the last dose of amphotericin B. On day 8, dogs were euthanatized and gross necropsies were performed. Unbiased semiquantitative scoring of the kidneys for the degree of injury was performed by use of light microscopy. RESULTS: There were no significant differences in serum creatinine, urea nitrogen, or potassium concentrations, urine specific gravity, endogenous creatinine clearance, or degree of tubulo-interstitial injury between the 2 groups. CONCLUSION: In this model, the degree of nephrotoxicity of amphotericin B was not significantly different for dogs receiving the drug in a fat emulsion versus its administration in 5% dextrose.

Amphotericin B↗

PubMed1995

Response to high-dose radioactive iodine administration in cats with thyroid carcinoma that had previously undergone surgery.

Seven cats with thyroid carcinomas that had previously undergone surgical removal of neoplastic tissue were treated with 30 mCi of radioactive iodine (131I). Six of the cats had clinical signs of hyperthyroidism; 1 did not. There were no complications associated with 131I treatment, and clinical signs resolved in all cats. Technetium scans of 4 cats made after treatment did not have evidence of isotope uptake. In the remaining 3 cats, small areas of isotope uptake, the intensity of which was equal to or less than the intensity of uptake in the salivary glands, were seen. All 7 cats became hypothyroid after treatment; 4 required L-thyroxine supplementation. One cat was alive 33 months after treatment. The other 6 cats were euthanatized because of unrelated diseases 10 to 41 months after treatment.

Adenocarcinoma, Follicular↗

PubMed1995

Treatment of nonregenerative anemia with human gamma-globulin in dogs.

Five dogs with nonregenerative anemia were treated with human immunoglobulin as a 12-hour IV infusion, at dosages ranging from 0.5 to 1.5 g/kg of body weight. All dogs had a rapid response to treatment, with reticulocytosis within 1 to 4 days and a substantial increase in hematocrit within 3 to 8 days of treatment. In 2 of 5 dogs, the hematocrit returned to values within reference range and remained in the reference range for 8 to 14 months after treatment, despite discontinuing or tapering prednisone treatment to a low dose. In 3 of 5 dogs, the hematocrit did not return to the reference range. In 1 of these 3 dogs, the hematocrit remained at the new, increased value (26 to 28%) for 248 days after treatment, at which time the dog was euthanatized. In the other 2 dogs, the hematocrit had decreased to pretreatment values by 52 days after treatment. Retreatment of these 2 dogs resulted in a similar, but blunted, response to human immunoglobulin. Human immunoglobulin may be an effective treatment for some dogs with immune-mediated anemia that fail to respond to conventional treatment.

Anemia, Hypochromic↗

PubMed1995

Ultrastructure and cytochemical staining characteristics of canine natural killer cells.

BACKGROUND: The purpose of this work was to describe the ultrastructure and cytochemical staining characteristics of canine peripheral blood lymphocytes with natural killer (NK) cell activity, with comparison made to non-NK lymphocytes. METHODS: Canine lymphocyte populations evaluated for ultrastructure, cytochemical staining, and NK function (by 51chromium release assay) included: peripheral blood lymphocytes; lymphocytes from band 1 (NK-enriched), band 2, and the pellet of a 45/50% percoll gradient; lymphocytes from the supernatant fluid (non-conjugated lymphocytes) and pellet (lymphocytes conjugated to tumor cell targets) of a 17% percoll gradient; and null (CD4-CD8-) and CD4-CD8+ lymphocytes. RESULTS: NK activity was concentrated in band 1 lymphocytes of the 45/50% percoll gradient with further enhancement of activity occurring in sorted null cells. Canine NK cells were 5.5 to 6.5 microns in diameter with a reniform (kidney bean shape) nucleus, and electron-dense cytoplasmic granules. NK cells (percoll band 1 cells and null cells) had larger cell and nuclear area, and less round nuclei when compared to non-NK lymphocytes. The overall cytochemical staining (chloracetate esterase, peroxidase, sudan black B, naphthyl acetate esterase, naphthyl butyrate esterase periodic acid-Schiff stain, and acid phosphatase with and without tartrate) pattern was similar in all the lymphocyte populations evaluated. CONCLUSIONS: This work confirms the usefulness of a 45/50% percoll gradient in obtaining a NK-enriched fraction of canine lymphocytes, and shows further enhancement of NK activity in sorted CD4- CD8- cells. The ultrastructure of canine NK cells is similar to that reported for human NK cells, but is different from that of other canine peripheral blood lymphocytes. Standard cytochemical staining does not discriminate canine NK cells from other lymphocytes.

Animals↗

PubMed1995

Biliary epithelial cell proliferation following alpha-naphthylisothiocyanate (ANIT) treatment: relationship to bile duct obstruction.

These studies were designed to evaluate the importance of bile duct obstruction in the pathogenesis of alpha-naphthylisothiocyanate (ANIT)-induced biliary epithelial cell (BEC) hyperplasia in rats. Hepatobiliary function and morphology were evaluated in adult male Sprague-Dawley rats 16, 24, 48, 72, 120, and 168 hr after a single oral dose of ANIT (0, 25, 75, or 150 mg/kg). After 75 or 150 mg/kg ANIT, multifocal bile duct obstruction was observed at 48 and 72 hr and preceded BEC hyperplasia which occurred at 120 and 168 hr. BEC proliferation, reflected by 5-bromo-2'-deoxyuridine (BrdU) incorporation, occurred at doses and at time points coinciding with BEC necrosis and/or bile duct obstruction. In contrast, 25 mg/kg ANIT produced minimal BEC damage and no evidence of bile duct obstruction or BEC hyperplasia. In a separate experiment, BEC proliferation was evaluated following bile duct ligation or ANIT treatment (150 mg/kg). The onset and peak of BEC proliferation occurred 24 and 48 hr, respectively, following bile duct obstruction resulting from either ligation or ANIT treatment. Furthermore, BEC proliferation occurred at all levels of the biliary tree in both bile duct-ligated and ANIT-treated rats. These data indicate that (a) dose-response curves for ANIT-induced bile duct obstruction and BEC hyperplasia are similar; (b) ANIT-induced BEC proliferation and bile duct obstruction precedes BEC hyperplasia; (c) BEC proliferation occurred at doses/timepoints associated with BEC damage and bile duct obstruction; and (d) once ANIT-induced bile duct obstruction occurs, the spatial and temporal aspects of BEC proliferation are comparable to those following biliary obstruction induced by bile duct ligation. Collectively, these data suggest that ANIT-induced BEC hyperplasia is secondary to intrahepatic bile duct obstruction.

1-Naphthylisothiocyanate↗