Uptake of drugs from topically applied anti-inflammatory preparations applied to racing animals

Objective To determine whether a drug detected in the blood or urine of a racing animal could have penetrated through the skin from a topically applied preparation.
Design Blood and urine of dogs and horses were analysed after topical administration of three common nonsteroidal anti-inflammatory preparations.
Experimental method Dimethylsulphoxide was analysed using a gas chromatograph with a flame photometric detector. Phenylbutazone, its metabolites and lignocaine were analysed using a gas chromatograph with a mass selective detector.
Results Dimethylsulphoxide, phenylbutazone and ligno-caine were detected in dog urine after muliple applications of the preparations. The maximum concentration of dimethyl-sulphoxide in dog urine correlated with the concentration of dimethylsulphoxide in the preparation. Phenylbutazone penetrated the skin more effectively from the cream than from the solution or gel preparations. This penetration was independent of the concentration of dimethylsulphoxide.
Conclusion The superior penetration of phenylbutazone from the cream can be explained by it being present as a neutral molecule in an hydrophobic medium. It is proposed that phenylbutazone penetrates the skin of greyhounds most effectively by a hydrophobic lipid route which is likely to be different from the path by which dimethylsulphoxide penetrates the skin.     

Electroporation Enhances Bleomycin Efficacy in Cats with Periocular Carcinoma and Advanced Squamous Cell Carcinoma of the Head

Background

Advanced carcinoma of the head represents a substantial health problem in cats for local control and overall survival.

Objectives

Evaluate the capability of electrochemotherapy (ECT) to improve bleomycin efficacy in cats with periocular carcinoma and advanced carcinoma of the head.

Animals

Twenty‐one cats with periocular carcinoma (17 squamous cell carcinoma [SCC] and 4 anaplastic carcinoma) and 26 cats with advanced SCC of the head.

Methods

Nonrandomized prospective controlled study. Periocular carcinoma cohorts: 12 cats were treated with bleomycin (15 mg/m² IV) coupled with ECT under anesthesia; 9 cats were treated with bleomycin alone. Advanced head SCC cohorts: 14 cats were treated with bleomycin (15 mg/m² IV) coupled with ECT administered under sedation; 12 control cats were treated with bleomycin alone. ECT treatments (2–8) were performed every other week until complete remission (CR) or tumor progression occurred.

Results

Toxicities were minimal and mostly treated symptomatically. Overall response rate in the ECT treated animals was 89% (21 Complete Response [CR] and 2 Partial Response [PR]) whereas controls had response rate of 33% (4 CR and 3 PR). Median time to progression in ECT group was 30.5 months, whereas in controls it was 3.9 months (P < .0001). Median time to progression for ECT cohorts was 24.2 months for periocular cohort and 20.6 in advanced head SCC cohort, respectively.

Conclusions

Electrochemotherapy is well tolerated for advanced SCC of the head in cats; its use may be considered among loco‐regional strategies for cancer therapy in sensitive body regions such as periocular region.     

Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles,Analogues of the Marine Alkaloid Nortopsentin

2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC₅₀ values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.     

Ventricular septal defect in a ferret (Mustela putorius furo)

A four-year-old, castrated male ferret (Mustela putorius furo) was evaluated because of a one-year history of sporadic cough. On physical examination a grade 5 of 6 holosystolic murmur was audible over the right apex of the heart. Radiographic findings included the presence of air bronchograms in apical lobes accompanied by pulmonary venous congestion. Colour Doppler echocardiography revealed a left-to-right shunting compatible with a ventricular septal defect. Medical therapy was initiated at the time of the diagnosis. The ferret was presented again 2 months after the initial examination for coughing and respiratory distress. Echocardiographic findings included tricuspid regurgitation, relative enlargement of left-atrial diameter and decreased systolic function, with presence of pleural effusion. Thoracocentesis was performed and the therapeutic plan was revised. In the following months the symptoms did not recur. In the authors' opinion this is the first report to describe the clinical findings of isolated ventricular septal defect in the ferret. Congenital heart defects are rare in this species, the present ferret being only the second case described.     

3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines,Nortopsentin Analogues with Antiproliferative Activity

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI₅₀ values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase.