Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy

BACKGROUND: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. AIM: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. ANIMALS: Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. METHODS: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. RESULTS: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. CONCLUSIONS AND CLINICAL IMPORTANCE: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.     

Discovery of a synergistic effect of oxytocin on the efficacy of Alpha-Chloralose,a drug used for capturing and controlling birds

Overdose and death of both target and non-target species are not uncommon when α–chloralose is used for animal control. Alpha–chloralose appears to depress the central nervous system by having an affect on the GABA-A receptor in a manner similar to ethanol. Recently central administration of oxytocin was shown to block ethanol-induced impairment in rodents. Our study investigates whether IM administration of oxytocin speeds avian recovery from α–chloralose and reduces mortality under simulated field conditions. We found that when injected twice with oxytocin (30 uL/kg) chickens entered α–chloralose narcosis more quickly and showed greater behavioral impairment. When fed the LD₅₀ dose of α–chloralose, repeated injection with oxytocin produced no significant difference in mortality rate or time to death in comparison to the control group. The effects of peripheral oxytocin on female chicks were different than results found previously in cockerels given oxytocin centrally. Oxytocin is not a suitable antidote for α–chloralose overdose during animal capture in the field but instead accentuates α–chloralose narcosis, making capture more likely and efficient.     

Content of retinol and retinyl esters in blood plasma,liver, kidney and reproductive organs of Japanese quails

Due to its importance in many physiological processes such as cell proliferation and differentiation, vitamin A plays a key role in reproduction. The present study examines the content and distribution of retinol and retinyl esters in the blood plasma, liver, kidney, ovary and oviduct (infundibulum, magnum, isthmus and uterus) of the laying Japanese quail. (1) The results show that the stage of egg laying had no influence on the level of vitamin A (retinol or retinyl esters) in plasma, kidney and liver. (2) The results further indicate that in the oviduct there are quantitative and qualitative differences in the concentration of retinol and retinyl esters, but that these differences are not altered by the stage of egg formation. (3) The highest levels of vitamin A in the isthmus and uterus were associated with a predominance of retinyl esters (palmitate and stearate); sections with lower total levels of vitamin A (infundibulum, magnum) had retinol as the more dominant form of vitamin A. (4) Changes in the ratio of retinol to retinyl esters in the various sections of the avian oviduct might point to metabolic differences. The storage of vitamin A might therefore be the predominant function of the uterus and isthmus; in the infundibulum and magnum, where vitamin A is predominantly present as retinol, vitamin A serves rather as a precursor for the modulation of the cellular metabolism of these structures.     

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores

The contents of retinol and retinyl esters as well as retinol-binding protein (RBP) in the plasma, urine, liver and kidneys of dogs, raccoon dogs and silver foxes were investigated. In the plasma and urine of all three species, vitamin A was present as retinol and retinyl esters. Vitamin A levels (1376+/-669 microg x g(-1)) were significantly higher in the livers of dogs than in the kidneys (200+/-217 microg x g(-1), P < 0.001 ). However, vitamin A levels in the kidneys of raccoon dogs (291+/-146 microg x g(-1)) and silver foxes (474+/-200 microg x g(-1)) were significantly higher than in the liver (67+/-58 microg x g(-1) and 4.3+/-2.4 microg x g(-1), respectively, both P < 0.001). RBP was immunologically detected in the blood plasma of all species, but never in the urine. In the liver, immunoreactive RBP was found in hepatocytes. In the kidneys of all species, RBP was observed in the cells of the proximal convoluted tubules. The levels of vitamin A in the livers of raccoon dogs and silver foxes were extremely low, which would be interpreted as a sign of great deficiency in humans. This observation might indicate that the liver status cannot be used as an indicator of vitamin A deficiency in canines. The high levels of vitamin A in the kidneys in all three species may indicate a specific function of the kidney in the vitamin A metabolism of canines.     

Evaluation of Bacillus thuringiensis Berliner as an alternative control of small hive beetles, Aethina tumida Murray (Coleoptera: Nitidulidae)

Small hive beetles, Aethina tumida Murray, are parasites and scavengers of honeybee colonies, Apis mellifera L., and have become an invasive species that can cause considerable damage in its new distribution areas. An effective subspecies of Bacillus thuringiensis Berliner (=Bt) would provide an alternative to chemical control of this pest. Therefore, we tested three different Bt strains [B. thuringiensis, var. aizawai (B401^®), B. thuringiensis var. kurstaki (Novodor^®) and B. thuringiensis var. San Diego tenebrionis (Jackpot^®)] and Perizin^® (3.2% coumaphos), each applied on combs with a pollen diet fed to pairs of adult beetles. This evaluates the products for the suppression of successful small hive beetle reproduction. While none of the tested Bt strains showed a significant effect on the number of produced wandering larvae, we could confirm the efficacy of coumaphos for the control of small hive beetles. We further show that it is also efficient when applied with a lower concentration as a liquid on the combs. We suggest the continued search for efficient Bt strains naturally infesting small hive beetles in its endemic and new ranges, which may become a part of the integrated management of this pest.     

Monensin controlled-release intraruminal capsule for control of bloat in pastured dairy cows

Monensin, a polyether ionophore antibiotic, is potentially an important agent for bloat relief in dairy cows grazing temperate legume-based pasture. A series of studies was undertaken to determine the effect of monensin, when delivered continuously in the rumen of lactating dairy cows by means of controlled-release capsules (monensin CRC). Such devices release approximately 300 mg/head/day for 100 d. A short-term pilot study made at Ruakura, New Zealand, tested monensin CRC in cows selected for high susceptibility to bloat and grazing lucerne (Medicago sativa) or red clover (Trifolium pratense). Treatment significantly reduced the incidence of bloat, while milk yield and protein yield were increased. There was no effect on fat yield. Following the pilot study, 6 large-scale field experiments involving a total of 368 lactating dairy cows, were made in Australia and New Zealand to confirm the effectiveness of monensin CRC for bloat control and to measure the effect of such treatment on milk production and composition. A severe bloat problem occurred in 2 experiments, mild bloat occurred in 2 others, while no visual signs of bloat were observed in the remaining 2 experiments. Bloat was significantly (P less than 0.05) reduced by monensin CRC treatment when data was pooled over the 4 experiments in which bloat occurred. Daily milk yield was increased in all experiments from a mean of 17.7 in untreated groups to 18.8 kg/head/day (P less than 0.05) in monensin CRC-treated cows. Protein percentage was not affected by treatment, while there was a decrease from 4.29 to 4.10% fat, although total fat yield was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Superior Check Desmotomy on Flexor Tendon and Suspensory Ligament Strain in Equine Cadaver Limbs

OBJECTIVE: To measure the effects of transection of the accessory ligament of the superficial digital flexor (SDF) muscle (superior check desmotomy) on flexor tendon and suspensory ligament (SL) strain in vitro. STUDY DESIGN: In vitro experimental biomechanical investigation. ANIMALS USED: Ten equine cadaver forelimbs. METHODS: The effects of superior check desmotomy were determined using equine cadaver forelimbs secured in a servocontrolled hydraulic testing machine. Strain sensors were used to measure strain on the superficial and deep digital flexor tendons and SL, and a goniometer was used to measure joint angles when the limb was loaded at 890 N and 3,115 N before desmotomy, and at 3,115 N after desmotomy. RESULTS: Superior check desmotomy was associated with significantly increased strains on the SDF tendon and SL, and significant alterations in the angles of the metacarpophalangeal and carpal joints. CONCLUSIONS: The superior check ligament has an important role in maintaining joint angles and load distribution in the forelimb. Lengthening of the SDF musculotendinous unit after superior check desmotomy may be associated with increased strain on the SL. CLINICAL RELEVANCE: Transection of the accessory ligament of the SDF muscle may predispose horses to SL desmitis postoperatively.